Kv1.5 potassium channel inhibitors

ABSTRACT

The present invention relates to 1-N-amino-2-imidazolidinones and derivatives thereof which are effective as Kv1.5 potassium channel inhibitors providing atrial-selective antiarrhythmic agents. The present invention further relates to compositions comprising said Kv1.5 potassium channel inhibitors, and to methods for treating cardiac arrhythmia.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/815,091 filed Jun. 20, 2006, which is herein incorporated byreference in its entirety

FIELD OF THE INVENTION

The present invention relates, inter alia, to compounds effective asKv1.5 potassium channel inhibitors. The present invention furtherrelates to inter alia, compositions comprising said Kv1.5 potassiumchannel inhibitors, and to methods for treating cardiac arrhythmia.

BACKGROUND OF THE INVENTION

Atrial fibrillation (AF) is the most frequently encountered cardiacarrhythmia in the clinical setting. It affects nearly 3 million peoplein the United States and its prevalence increases with the aging of thepopulation. AF is most often treated with class III antiarrhythmicagents, acting at both the atrial and ventricular levels. Commonly usedor prescribed antiarrhythmic drugs inhibit various potassium channels,and prolong ventricular repolarization. This prolongation can in turnprecipitate the occurrence of life-threatening-ventricular arrhythmias,mainly Torsades de Pointes (TdP).

Atrial-selective antiarrhythmic agents offer the possibility ofincreased therapeutic efficacy and safety by minimizing cardiacproarrhythmia inherent in traditional antiarrhythmic therapies.

There is therefore a long felt need for atrial-selective antiarrhythmicagents which do not affect ventricular rhythm. In addition, there is along felt need for atrial-selective antiarrhythmic agents which arecompatible with other cardiac devices, protocols, therapies, andmedications. The present invention addresses this and other needs.

SUMMARY OF THE INVENTION

The 1-N-amino-2-imidazolidinones of the present invention are a newclass of compounds. Compounds of this class have been found to inhibitKv1.5 potassium channels function.

Exemplary compounds of the present invention have formula (I):

wherein R is optionally substituted phenyl;R¹ is optionally substituted phenyl, optionally substituted C₁-C₆ linearor branched alkyl, optionally substituted C₃-C₇ cycloalkyl, oroptionally substituted heteroaryl;R^(1a) is hydrogen or C₁-C₆ linear or branched alkyl;R² is hydrogen or is selected from

-   -   i) —SO₂[C(R^(5a)R^(5b))]_(j)R⁴;    -   ii) —C(O)[C(R^(5a)R^(5b))]_(k)R⁴; or    -   iii) —[C(R^(5a)R^(5b))]_(n)R⁴;        R³ is hydrogen or is selected from:    -   i) C₁-C₄ linear or branched alkyl, or C₃-C₇ cycloalkyl;    -   ii) —SO₂[C(R^(5a)R^(5b))]_(j)R⁴; or    -   iii) —[C(R^(5a)R^(5b))]_(n)R⁴; or        R² and R³ are taken together with the atom to which they are        bound to form an optionally substituted ring having from 3 to 7        ring atoms optionally containing one or more additional        heteroatom ring atoms selected from N, O, or S;        R^(5a) and R^(5b) are each independently hydrogen or C₁-C₄        linear alkyl;        R⁴ is selected from;    -   i) hydrogen;    -   ii) —N(R^(6a)R^(6b));    -   iii) —SO₂R⁷;    -   iv) —C(O)N(R^(8a)R^(8b));    -   v) optionally substituted C₁-C₆ linear or branched alkyl, or        optionally substituted C₃-C₆ cycloalkyl;    -   vi) optionally substituted C₂-C₆ linear or branched alkenyl;    -   vii) optionally substituted C₁-C₆ linear or branched alkoxy;    -   viii) optionally substituted C₆ or C₁₀ aryl;    -   ix) optionally substituted C₆ or C₁₀ aryloxy;    -   x) optionally substituted heteroaryl;    -   xi) optionally substituted heterocycle; or    -   xii) optionally substituted C(O)O(arylalkyl);        R^(6a) and R^(6b) are each independently hydrogen, optionally        substituted C₁-C₆ linear or branched alkyl, optionally        substituted C₃-C₆ cycloalkyl, optionally substituted benzyl,        optionally substituted phenyl, or —C(O)OR^(7a), or R^(6a) and        R^(6b) are taken together with the atom to which they are bound        to form a ring having from 3 to 7 ring atoms optionally        containing one or more additional heteroatom ring atoms selected        from N, O, or S;        R⁷ is hydrogen, optionally substituted C₁-C₆ linear or branched        alkyl, optionally substituted C₃-C₆ cycloalkyl, or N(R^(7a))₂;        R^(7a) at each occurrence, independently, is hydrogen,        optionally substituted C₁-C₆ linear or branched alkyl, or        optionally substituted C₃-C₆ cycloalkyl;        R^(8a) and R^(8b) are each independently hydrogen, optionally        substituted C₁-C₆ linear or branched alkyl, optionally        substituted C₃-C₆ cycloalkyl, or R^(8a) and R^(8b) are taken        together with the atom to which they are bound to form a ring        having from 3 to 7 ring atoms optionally containing one or more        additional heteroatom ring atoms selected from N, O, or S;        L and L¹ are, independently, —[C(R^(9a)R^(9b))]_(m)—;        R^(9a) and R^(9b) are, at each occurrence, each independently        hydrogen or methyl, or R^(9a) and        R^(9b) are taken together with the atom to which they are bound        to form a cyclopropyl ring;        x and y are independently 0 or 1;        m, at each occurrence, independently is 0 to 4;        j, at each occurrence, independently is 0 to 4; and        k and n, at each occurrence, are independently 0 to 3; or a        pharmaceutically acceptable salt form thereof.

The compounds of the present invention include compounds having formula(II):

wherein R is phenyl or substituted phenyl;R¹ is phenyl or substituted phenyl;R² is hydrogen or is selected from:

-   -   ii) —SO₂[C(R^(5a)R^(5b))]_(j)R⁴;    -   ii) —C(O)[C(R^(5a)R^(5b))]_(k)R⁴; or    -   iii) —[C(R^(5a)R^(5b))]_(n)R⁴;

R³ is hydrogen or is selected from:

-   -   i) C₁-C₄ linear or branched alkyl, or C₃-C₄ cycloalkyl;    -   ii) —SO₂[C(R^(5a)R^(5b))]_(j)R⁴; or    -   iii) —[C(R^(5a)R^(5b))]_(n)R⁴; or        R² and R³ are taken together with the atom to which they are        bound to form an optionally substituted ring having from 3 to 7        ring atoms optionally containing one or more additional        heteroatom ring atoms selected from N, O, or S;        R^(5a) and R^(5b) are each independently hydrogen or C₁-C₄        linear alkyl;        R⁴ is selected from;    -   i) hydrogen;    -   ii) —N(R^(6a)R^(6b));    -   iii) —SO₂R⁷;    -   iv) —C(O)N(R^(8a)R^(8b));    -   v) optionally substituted C₁-C₆ linear or branched alkyl, or        optionally substituted C₃-C₆ cycloalkyl;    -   vi) optionally substituted C₂-C₆ linear or branched alkenyl;    -   vii) optionally substituted C₁-C₆ linear or branched alkoxy or        optionally substituted C₃-C₆ cyclic alkoxy;    -   viii) optionally substituted C₆ or C₁₀ aryl;    -   ix) optionally substituted C₆ or C₁₀ aryloxy;    -   x) optionally substituted C₁-C₁₀ heteroaryl; or    -   xi) optionally substituted C₁-C₁₀ heterocycle; or        R^(6a) and R^(6b) are each independently hydrogen, optionally        substituted C₁-C₆ linear or branched alkyl, optionally        substituted C₃-C₆ cycloalkyl, optionally substituted benzyl, or        —C(O)OR⁷, or R^(6a) and R^(6b) are taken together with the atom        to which they are bound to form a ring having from 3 to 7 ring        atoms optionally containing one or more additional heteroatom        ring atoms selected from N, O, or S;        R⁷ is hydrogen, optionally substituted C₁-C₆ linear or branched        alkyl, optionally substituted C₃-C₆ cycloalkyl, NH₂, —NH(C₁-C₄        alkyl), or —N(C₁-C₄ alkyl)₂;        R^(8a) and R^(8b) are each independently hydrogen, optionally        substituted C₁-C₆ linear or branched alkyl, optionally        substituted C₃-C₆ cycloalkyl, or R^(8a) and R^(8b) are taken        together with the atom to which they are bound to form a ring        having from 3 to 7 ring atoms optionally containing one or more        additional heteroatom ring atoms selected from N, O, or S;        L is —[C(R^(9a)R^(9b))]_(m)—;        R^(9a) and R^(9b) are each independently hydrogen or methyl;        x and y are independently 0 or 1;        m is 0 to 4;        j is 1 to 4; and        k and n are independently 0 to 3; or a pharmaceutically        acceptable salt form thereof.

The present invention further relates to compositions comprising: aneffective amount of one or more compounds according to the presentinvention and an excipient.

The present invention also relates to a method for treating orpreventing cardiac arrhythmias, including, for example, atrialfibrillation and atrial flutter, said method comprising administering toa subject an effective amount of a compound or composition according tothe present invention.

The present invention yet further relates to a method for treating orpreventing cardiac arrhythmias, including, for example, atrialfibrillation or flutter, wherein said method comprises administering toa subject a composition comprising an effective amount of one or morecompounds according to the present invention and an excipient.

The present invention also relates to a method for treating orpreventing disease or conditions associated with cardiac arrhythmias,including, for example, thromboembolism, stroke, and heart failure. Saidmethods comprise administering to a subject an effective amount of acompound or composition according to the present invention.

The present invention yet further relates to a method for treating orpreventing disease or conditions associated with cardiac arrhythmias,including, for example, thromboembolism, stroke, and heart failure,wherein said method comprises administering to a subject a compositioncomprising an effective amount of one or more compounds according to thepresent invention and an excipient.

The present invention also relates to a compound of the presentinvention for use in therapy, and to the use of a compound of thepresent invention for the manufacture of a medicament for treating orpreventing conditions mentioned herein.

The present invention further relates to a process for preparing theKv1.5 potassium channel inhibitors of the present invention.

These and other objects, features, and advantages will become apparentto those of ordinary skill in the art from a reading of the followingdetailed description and the appended claims. All percentages, ratiosand proportions herein are by weight, unless otherwise specified. Alltemperatures are in degrees Celsius (° C.) unless otherwise specified.All documents cited are in relevant part, incorporated herein byreference; the citation of any document is not to be construed as anadmission that it is prior art with respect to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The Kv1.5 potassium channel inhibitors of the present invention arecapable of selectively preventing arrhythmia in the atrial portion ofthe human heart or in the heart of certain animals. It has beendiscovered that functional Kv1.5 potassium channels are found in humanatrial tissue but not in human ventricular myocytes. Without wishing tobe limited by theory, it is believed the selective inhibition of theKv1.5 voltage-gated Shaker-like potassium (K⁺) ion channel canameliorate, abate, or otherwise cause to be controlled, atrialfibrillation/flutter without prolonging ventricular repolarization.

Throughout the description, where compositions are described as having,including, or comprising specific components, or where processes aredescribed as having, including, or comprising specific process steps, itis contemplated that compositions of the present teachings also consistessentially of, or consist of, the recited components, and that theprocesses of the present teachings also consist essentially of, orconsist of, the recited processing steps.

In the application, where an element or component is said to be includedin and/or selected from a list of recited elements or components, itshould be understood that the element or component can be any one of therecited elements or components and can be selected from a groupconsisting of two or more of the recited elements or components.

The use of the singular herein includes the plural (and vice versa)unless specifically stated otherwise. In addition, where the use of theterm “about” is before a quantitative value, the present teachings alsoinclude the specific quantitative value itself, unless specificallystated otherwise.

It should be understood that the order of steps or order for performingcertain actions is immaterial so long as the present teachings remainoperable. Moreover, two or more steps or actions can be conductedsimultaneously

As used herein, unless otherwise noted, “alkyl” whether used alone or aspart of a substituent group refers to straight and branched carbonchains having 1 to 20 carbon atoms or any number within this range, forexample 1 to 6 carbon atoms or 1 to 4 carbon atoms. Designated numbersof carbon atoms (e.g. C₁₋₆) shall refer independently to the number ofcarbon atoms in an alkyl moiety or to the alkyl portion of a largeralkyl-containing substituent. Non-limiting examples of alkyl groupsinclude methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl,iso-butyl, tert-butyl, and the like. Alkyl groups can be optionallysubstituted. Non-limiting examples of substituted alkyl groups includehydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl,1-chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, 3-carboxypropyl, andthe like. In substituent groups with multiple alkyl groups such as(C₁₋₆alkyl)₂amino, the alkyl groups may be the same or different.

As used herein, the terms “alkenyl” and “alkynyl” groups, whether usedalone or as part of a substituent group, refer to straight and branchedcarbon chains having 2 or more carbon atoms, preferably 2 to 20, whereinan alkenyl chain has at least one double bond in the chain and analkynyl chain has at least one triple bond in the chain. Alkenyl andalkynyl groups can be optionally substituted. Nonlimiting examples ofalkenyl groups include ethenyl, 3-propenyl, 1-propenyl (also2-methylethenyl), isopropenyl (also 2-methylethen-2-yl), buten-4-yl, andthe like. Nonlimiting examples of substituted alkenyl groups include2-chloroethenyl (also 2-chlorovinyl), 4-hydroxybuten-1-yl,7-hydroxy-7-methyloct-4-en-2-yl, 7-hydroxy-7-methyloct-3,5-dien-2-yl,and the like. Nonlimiting examples of alkynyl groups include ethynyl,prop-2-ynyl (also propargyl), propyn-1-yl, and 2-methyl-hex-4-yn-1-yl.Nonlimiting examples of substituted alkynyl groups include,5-hydroxy-5-methylhex-3-ynyl, 6-hydroxy-6-methylhept-3-yn-2-yl,5-hydroxy-5-ethylhept-3-ynyl, and the like.

As used herein, “cycloalkyl,” whether used alone or as part of anothergroup, refers to a non-aromatic carbon-containing ring includingcyclized alkyl, alkenyl, and alkynyl groups, e.g., having from 3 to 14ring carbon atoms, preferably from 3 to 7 or 3 to 6 ring carbon atoms,or even 3 to 4 ring carbon atoms, and optionally containing one or more(e.g., 1, 2, or 3) double or triple bond. Cycloalkyl groups can bemonocyclic (e.g., cyclohexyl) or polycyclic (e.g., containing fused,bridged, and/or spiro ring systems), wherein the carbon atoms arelocated inside or outside of the ring system. Any suitable ring positionof the cycloalkyl group can be covalently linked to the defined chemicalstructure. Cycloalkyl rings can be optionally substituted. Nonlimitingexamples of cycloalkyl groups include: cyclopropyl,2-methyl-cyclopropyl, cyclopropenyl, cyclobutyl,2,3-dihydroxycyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl,cyclopentadienyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctanyl,decalinyl, 2,5-dimethylcyclopentyl, 3,5-dichlorocyclohexyl,4-hydroxycyclohexyl, 3,3,5-trimethylcyclohex-1-yl, octahydropentalenyl,octahydro-1H-indenyl, 3a,4,5,6,7,7a-hexahydro-3H-inden-4-yl,decahydroazulenyl; bicyclo[6.2.0]decanyl, decahydronaphthalenyl, anddodecahydro-1H-fluorenyl. The term “cycloalkyl” also includescarbocyclic rings which are bicyclic hydrocarbon rings, non-limitingexamples of which include, bicyclo-[2.1.1]hexanyl,bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl,1,3-dimethyl[2.2.1]heptan-2-yl, bicyclo[2.2.2]octanyl, andbicyclo[3.3.3]undecanyl.

“Haloalkyl” is intended to include both branched and straight-chainsaturated aliphatic hydrocarbon groups having the specified number ofcarbon atoms, substituted with 1 or more halogen. Haloalkyl groupsinclude perhaloalkyl groups, wherein all hydrogens of an alkyl grouphave been replaced with halogens (e.g., —CF₃, —CF₂CF₃). Haloalkyl groupscan optionally be substituted with one or more substituents in additionto halogen. Examples of haloalkyl groups include, but are not limitedto, fluoromethyl, dichloroethyl, trifluoromethyl, trichloromethyl,pentafluoroethyl, and pentachloroethyl groups.

The term “alkoxy” refers to the group —O-alkyl, wherein the alkyl groupis as defined above. Alkoxy groups optionally may be substituted. Theterm C₃-C₆ cyclic alkoxy refers to a ring containing 3 to 6 carbon atomsand at least one oxygen atom (e.g., tetrahydrofuran,tetrahydro-2H-pyran). C₃-C₆ cyclic alkoxy groups optionally may besubstituted.

The term “aryl,” wherein used alone or as part of another group, isdefined herein as a an unsaturated, aromatic monocyclic ring of 6 carbonmembers or to an unsaturated, aromatic polycyclic ring of from 10 to 14carbon members. Aryl rings can be, for example, phenyl or naphthyl ringeach optionally substituted with one or more moieties capable ofreplacing one or more hydrogen atoms. Non-limiting examples of arylgroups include: phenyl, naphthylen-1-yl, naphthylen-2-yl,4-fluorophenyl, 2-hydroxyphenyl, 3-methylphenyl, 2-amino-4-fluorophenyl,2-(N,N-diethylamino)phenyl, 2-cyanophenyl, 2,6-di-tert-butylphenyl,3-methoxyphenyl, 8-hydroxynaphthylen-2-yl 4,5-dimethoxynaphthylen-1-yl,and 6-cyano-naphthylen-1-yl. Aryl groups also include, for example,phenyl or naphthyl rings fused with one or more saturated or partiallysaturated carbon rings (e.g., bicyclo[4.2.0]octa-1,3,5-trienyl,indanyl), which can be substituted at one or more carbon atoms of thearomatic and/or saturated or partially saturated rings.

The term “arylalkyl” or “aralkyl” refers to the group -alkyl-aryl, wherethe alkyl and aryl groups are as defined herein. Aralkyl groups of thepresent invention are optionally substituted. Examples of arylalkylgroups include, for example, benzyl, 1-phenylethyl, 2-phenylethyl,3-phenylpropyl, 2-phenylpropyl, fluorenylmethyl and the like.

The terms “heterocyclic” and/or “heterocycle,” whether used alone or aspart of another group, are defined herein as one or more rings (e.g., 2or 3 rings) having from 3 to 20 atoms wherein at least one atom in atleast one ring is a heteroatom selected from nitrogen (N), oxygen (O),or sulfur (S), and wherein further the ring that includes the heteroatomis non-aromatic. In heterocycle groups that include 2 or more fusedrings, the non-heteroatom bearing ring may be aryl (e.g., indolinyl,tetrahydroquinolinyl, chromanyl). Exemplary heterocycle groups have from3 to 14 ring atoms of which from 1 to 5 are heteroatoms independentlyselected from nitrogen (N), oxygen (O), or sulfur (S). One or more N orS atoms in a heterocycle group can be oxidized. Heterocycle groups canbe optionally substituted.

Non-limiting examples of heterocyclic units having a single ringinclude: diazirinyl, aziridinyl, urazolyl, azetidinyl, pyrazolidinyl,imidazolidinyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolidinyl,isothiazolyl, isothiazolinyl oxathiazolidinonyl, oxazolidinonyl,hydantoinyl, tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperazinyl,piperidinyl, dihydropyranyl, tetrahydropyranyl, piperidin-2-onyl(valerolactam), 2,3,4,5-tetrahydro-1H-azepinyl, 2,3-dihydro-1H-indole,and 1,2,3,4-tetrahydro-quinoline. Non-limiting examples of heterocyclicunits having 2 or more rings include: hexahydro-1H-pyrrolizinyl,3a,4,5,6,7,7a-hexahydro-1H-benzo[d]imidazolyl,3a,4,5,6,7,7a-hexahydro-1H-indolyl, 1,2,3,4-tetrahydroquinolinyl,chromanyl, isochromanyl, indolinyl, isoindolinyl, anddecahydro-1H-cycloocta[b]pyrrolyl.

The term “heteroaryl,” whether used alone or as part of another group,is defined herein as one or more rings having from 5 to 20 atoms whereinat least one atom in at least one ring is a heteroatom chosen fromnitrogen (N), oxygen (O), or sulfur (S), and wherein further at leastone of the rings that includes a heteroatom is aromatic. In heteroarylgroups that include 2 or more fused rings, the non-heteroatom bearingring may be a carbocycle (e.g., 6,7-Dihydro-5H-cyclopentapyrimidine) oraryl (e.g., benzofuranyl, benzothiophenyl, indolyl). Exemplaryheteroaryl groups have from 5 to 14 ring atoms and contain from 1 to 5ring heteroatoms independently selected from nitrogen (N), oxygen (O),or sulfur (S). One or more N or S atoms in a heteroaryl group can beoxidized. Heteroaryl groups can be substituted. Non-limiting examples ofheteroaryl rings containing a single ring include: 1,2,3,4-tetrazolyl,[1,2,3]triazolyl, [1,2,4]triazolyl, triazinyl, thiazolyl, 1H-imidazolyl,oxazolyl, furanyl, thiopheneyl, pyrimidinyl, 2-phenylpyrimidinyl,pyridinyl, 3-methylpyridinyl, and 4-dimethylaminopyridinyl. Non-limitingexamples of heteroaryl rings containing 2 or more fused rings include:benzofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl,benztriazolyl, cinnolinyl, naphthyridinyl, phenanthridinyl, 7H-purinyl,9H-purinyl, 6-amino-9H-purinyl, 5H-pyrrolo[3,2-d]pyrimidinyl,7H-pyrrolo[2,3-d]pyrimidinyl, pyrido[2,3-d]pyrimidinyl,2-phenylbenzo[d]thiazolyl, 1H-indolyl, 4,5,6,7-tetrahydro-1-H-indolyl,quinoxalinyl, 5-methylquinoxalinyl, quinazolinyl, quinolinyl,8-hydroxy-quinolinyl, and isoquinolinyl.

One non-limiting example of a heteroaryl group as described above isC₁-C₅ heteroaryl, which has 1 to 5 carbon ring atoms and at least oneadditional ring atom that is a heteroatom (preferably 1 to 4 additionalring atoms that are heteroatoms) independently selected from nitrogen(N), oxygen (O), or sulfur (S). Examples of C₁-C₅ heteroaryl include,but are not limited to, triazinyl, thiazol-2-yl, thiazol-4-yl,imidazol-1-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, isoxazolin-5-yl,furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-4-yl, pyrimidin-2-yl,pyrimidin-4-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-3-yl, andpyridin-4-yl.

Unless otherwise noted, when two substituents are taken together to forma ring having a specified number of ring atoms (e.g., R² and R³ takentogether with the N to which they are attached to form a ring havingfrom 3 to 7 ring members), the ring can have carbon atoms and optionallyone or more (e.g., 1 to 3) additional heteroatoms independently selectedfrom nitrogen (N), oxygen (O), or sulfur (S). The ring can be saturatedor partially saturated and can be optionally substituted.

The terms “treat” and “treating,” as used herein, refer to partially orcompletely alleviating, inhibiting, ameliorating and/or relieving acondition from which a patient is suspected to suffer.

As used herein, “therapeutically effective” refers to a substance or anamount that elicits a desirable biological activity or effect.

Except when noted, the terms “subject” or “patient” are usedinterchangeably and refer to mammals such as human patients andnon-human primates, as well as experimental animals such as rabbits,rats, and mice, and other animals. Accordingly, the term “subject” or“patient” as used herein means any mammalian patient or subject to whichthe compounds of the invention can be administered. In an exemplaryembodiment of the present invention, to identify subject patients fortreatment according to the methods of the invention, accepted screeningmethods are employed to determine risk factors associated with atargeted or suspected disease or condition or to determine the status ofan existing disease or condition in a subject. These screening methodsinclude, for example, conventional work-ups to determine risk factorsthat may be associated with the targeted or suspected disease orcondition. These and other routine methods allow the clinician to selectpatients in need of therapy using the methods and compounds of thepresent invention.

For the purposed of the present invention fused ring units, as well asspirocyclic rings, bicyclic rings and the like, which comprise a singleheteroatom will be considered to belong to the cyclic familycorresponding to the heteroatom containing ring. For example,1,2,3,4-tetrahydroquinoline having the formula:

is, for the purposes of the present invention, considered a heterocyclicunit. 6,7-Dihydro-5H-cyclopentapyrimidine having the formula:

is, for the purposes of the present invention, considered a heteroarylunit. When a fused ring unit contains heteroatoms in both a saturatedand an aryl ring, the aryl ring will predominate and determine the typeof category to which the ring is assigned. For example,1,2,3,4-tetrahydro-[1,8]naphthyridine having the formula:

is, for the purposes of the present invention, considered a heteroarylunit.

Whenever a term or either of their prefix roots appear in a name of asubstituent the name is to be interpreted as including those limitationsprovided herein. For example, whenever the term “alkyl” or “aryl” oreither of their prefix roots appear in a name of a substituent (e.g.,arylalkyl, alkylamino) the name is to be interpreted as including thoselimitations given above for “alkyl” and “aryl.”

The term “substituted” is used throughout the specification. The term“substituted” is defined herein as a moiety, whether acyclic or cyclic,which has one or more hydrogen atoms replaced by a substituent orseveral (e.g., 1 to 10) substituents as defined herein below. Thesubstituents are capable of replacing one or two hydrogen atoms of asingle moiety at a time. In addition, these substituents can replace twohydrogen atoms on two adjacent carbons to form said substituent, newmoiety or unit. For example, a substituted unit that requires a singlehydrogen atom replacement includes halogen, hydroxyl, and the like. Atwo hydrogen atom replacement includes carbonyl, oximino, and the like.A two hydrogen atom replacement from adjacent carbon atoms includesepoxy, and the like. The term “substituted” is used throughout thepresent specification to indicate that a moiety can have one or more ofthe hydrogen atoms replaced by a substituent. When a moiety is describedas “substituted” any number of the hydrogen atoms may be replaced. Forexample, difluoromethyl is a substituted C₁ alkyl; trifluoromethyl is asubstituted C₁ alkyl; 4-hydroxyphenyl is a substituted aromatic ring;(N,N-dimethyl-5-amino)octanyl is a substituted C₈ alkyl;3-guanidinopropyl is a substituted C₃ alkyl; and 2-carboxypyridinyl is asubstituted heteroaryl.

The variable groups defined herein, e.g., alkyl, alkenyl, alkynyl,cycloalkyl, alkoxy, aryloxy, aryl, heterocycle and heteroaryl groupsdefined herein, whether used alone or as part of another group, can beoptionally substituted. Optionally substituted groups will be soindicated.

The following are non-limiting examples of substituents which cansubstitute for hydrogen atoms on a moiety: halogen (F, Cl, Br, I), —CN,—NO₂, oxo (═O), —OR¹⁵, —SR¹⁵, —N(R¹⁵)₂, —NR¹⁵C(O)R¹⁵, —SO₂R¹⁵, —SO₂OR¹⁵,—SO₂N(R¹⁵)₂, —C(O)R¹⁵, —C(O)OR¹⁵, —C(O)N(R¹⁵)₂, C₁₋₆ alkyl, C₁₋₆haloalkyl, C₁₋₆ alkoxy, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₁₄ cycloalkyl,aryl, heterocycle, or heteroaryl, wherein each of the alkyl, haloalkyl,alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocycle, and heteroarylgroups is optionally substituted with 1-10 (e.g., 1-6 or 1-4) groupsselected independently from halogen, —CN, —NO₂, oxo, and R¹⁵; whereinR¹⁵, at each occurrence, independently is hydrogen, —OR¹⁶, —SR¹⁶,—C(O)R¹⁶, —C(O)OR¹⁶, —C(O)N(R¹⁶)₂, —SO₂R¹⁶, —S(O)₂OR¹⁶, —N(R¹⁶)₂,—NR¹⁶C(O)R¹⁶, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,cycloalkyl (e.g., C₃₋₆ cycloalkyl), aryl, heterocycle, or heteroaryl, ortwo R¹⁵ units taken together with the atom(s) to which they are boundform an optionally substituted carbocycle or heterocycle wherein saidcarbocycle or heterocycle has 3 to 7 ring atoms; wherein R¹⁶, at eachoccurrence, independently is hydrogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₈alkenyl, C₂₋₈ alkynyl, cycloalkyl (e.g., C₃₋₆ cycloalkyl), aryl,heterocycle, or heteroaryl, or two R¹⁶ units taken together with theatom(s) to which they are bound form an optionally substitutedcarbocycle or heterocycle wherein said carbocycle or heterocyclepreferably has 3 to 7 ring atoms.

In some embodiments, the substituents are selected from

-   -   i) —OR¹⁷; for example, —OH, —OCH₃, —OCH₂CH₃, —OCH₂CH₂CH₃;    -   ii) —C(O)R¹⁷; for example, —COCH₃, —COCH₂CH₃, —COCH₂CH₂CH₃;    -   iii) —C(O)OR¹⁷; for example, —CO₂CH₃, —CO₂CH₂CH₃, —CO₂CH₂CH₂CH₃;    -   iv) —C(O)N(R¹⁷)₂; for example, —CONH₂, —CONHCH₃, —CON(CH₃)₂;    -   v) —N(R¹⁷)₂; for example, —NH₂, —NHCH₃, —N(CH₃)₂, —NH(CH₂CH₃);    -   vi) halogen: —F, —Cl, —Br, and —I;    -   vii) —CH_(m)X_(n); wherein X is halogen, m is from 0 to 2,        m+n=3; for example, —CH₂F, —CHF₂, —CF₃, —CCl₃, or —CBr₃;    -   viii) —SO₂R¹⁷; for example, —SO₂H; —SO₂CH₃; —SO₂C₆H₅;    -   ix) C₁-C₆ linear, branched, or cyclic alkyl;    -   x) Cyano    -   xi) Nitro;    -   xii) N(R¹⁷)C(O)R¹⁷;    -   xiii) Oxo (═O);    -   xiv) Heterocycle; and    -   xv) Heteroaryl.        wherein each R¹⁷ is independently hydrogen, optionally        substituted C₁-C₆ linear or branched alkyl (e.g., optionally        substituted C₁-C₄ linear or branched alkyl), or optionally        substituted C₃-C₆ cycloalkyl (e.g optionally substituted C₃-C₄        cycloalkyl); or two R¹⁷ units can be taken together to form a        ring comprising 3-7 ring atoms. In certain aspects, each R¹⁷ is        independently hydrogen, C₁-C₆ linear or branched alkyl        optionally substituted with halogen or C₃-C₆ cycloalkyl or C₃-C₆        cycloalkyl.

At various places in the present specification, substituents ofcompounds are disclosed in groups or in ranges. It is specificallyintended that the description include each and every individualsubcombination of the members of such groups and ranges. For example,the term “C₁₋₆ alkyl” is specifically intended to individually discloseC₁, C₂, C₃, C₄, C₅, C₆, C₁-C₆, C₁-C₅, C₁-C₄, C₁-C₃, C₁-C₂, C₂-C₆, C₂-C₅,C₂-C₄, C₂-C₃, C₃-C₆, C₃-C₅, C₃-C₄, C₄-C₆, C₄-C₅, and C₅-C₆, alkyl.

For the purposes of the present invention the terms “compound,”“analog,” and “composition of matter” stand equally well for the Kv1.5potassium channel inhibitors described herein, including allenantiomeric forms, diastereomeric forms, salts, and the like, and theterms “compound,” “analog,” and “composition of matter” are usedinterchangeably throughout the present specification.

Compounds described herein can contain an asymmetric atom (also referredas a chiral center), and some of the compounds can contain one or moreasymmetric atoms or centers, which can thus give rise to optical isomers(enantiomers) and diastereomers. The present teachings and compoundsdisclosed herein include such enantiomers and diastereomers, as well asthe racemic and resolved, enantiomerically pure R and S stereoisomers,as well as other mixtures of the R and S stereoisomers andpharmaceutically acceptable salts thereof. Optical isomers can beobtained in pure form by standard procedures known to those skilled inthe art, which include, but are not limited to, diastereomeric saltformation, kinetic resolution, and asymmetric synthesis. The presentteachings also encompass cis and trans isomers of compounds containingalkenyl moieties (e.g., alkenes and imines). It is also understood thatthe present teachings encompass all possible regioisomers, and mixturesthereof, which can be obtained in pure form by standard separationprocedures known to those skilled in the art, and include, but are notlimited to, column chromatography, thin-layer chromatography, andhigh-performance liquid chromatography.

Pharmaceutically acceptable salts of compounds of the present teachings,which can have an acidic moiety, can be formed using organic andinorganic bases. Both mono and polyanionic salts are contemplated,depending on the number of acidic hydrogens available for deprotonation.Suitable salts formed with bases include metal salts, such as alkalimetal or alkaline earth metal salts, for example sodium, potassium, ormagnesium salts; ammonia salts and organic amine salts, such as thoseformed with morpholine, thiomorpholine, piperidine, pyrrolidine, amono-, di- or tri-lower alkylamine (e.g., ethyl-tert-butyl-, diethyl-,diisopropyl-, triethyl-, tributyl- or dimethylpropylamine), or a mono-,di-, or trihydroxy lower alkylamine (e.g., mono-, di- ortriethanolamine). Specific non-limiting examples of inorganic basesinclude NaHCO₃, Na₂CO₃, KHCO₃, K₂CO₃, Cs₂CO₃, LiOH, NaOH, KOH, NaH₂PO₄,Na₂HPO₄, and Na₃PO₄. Internal salts also can be formed. Similarly, whena compound disclosed herein contains a basic moiety, salts can be formedusing organic and inorganic acids. For example, salts can be formed fromthe following acids: acetic, propionic, lactic, benzenesulfonic,benzoic, camphorsulfonic, citric, tartaric, succinic, dichloroacetic,ethenesulfonic, formic, fumaric, gluconic, glutamic, hippuric,hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, malonic,mandelic, methanesulfonic, mucic, napthalenesulfonic, nitric, oxalic,pamoic, pantothenic, phosphoric, phthalic, propionic, succinic,sulfuric, tartaric, toluenesulfonic, and camphorsulfonic as well asother known pharmaceutically acceptable acids.

When any variable occurs more than one time in any constituent or in anyformula, its definition in each occurrence is independent of itsdefinition at every other occurrence (e.g., in N(R¹⁵)₂, each R¹⁵ may bethe same or different than the other). Combinations of substituentsand/or variables are permissible only if such combinations result instable compounds.

Kv1.5 Potassium Channel Inhibitors

The Kv1.5 potassium channel inhibitors of the present invention are2-imidazoli-dinones, and include all enantiomeric and diastereomericforms and salts thereof having the formula:

wherein the core scaffold is numbered in the following manner;

For the purposes of demonstrating the manner in which the compounds ofthe present invention are named and referred to herein, the compoundhaving the formula:

has the chemical name4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-[(pyridin-2-ylmethyl)amino]-imidazolidin-2-one.

For the purposes of the present invention, a compound depicted by theracemic formula, for example:

will stand equally well for either of the two enantiomers having theformula:

or the formula:

or in the case where a second chiral center is present, alldiastereomers. However, the term 1-N-amino-2-imidazolidinones is used ingeneral to refer to the genus, which encompasses the compounds of thepresent invention, throughout the specification.

The particular embodiments and illustrations herein relating toparticular aspects of the present invention may be combined in thecompounds of the present invention.

In the present invention, R is optionally substituted phenyl. The phenylgroup can be substituted with any of the substituents provided herein.Examples of suitable substituents include, but are not limited tohalogen, optionally substituted C₁-C₆ linear or branched alkyl,optionally substituted C₁-C₆ linear or branched haloalkyl, optionallysubstituted C₃-C₆ cycloalkyl, —OR¹³, —CN, —N(R¹³)₂, —CO₂R¹³,—C(O)N(R¹³)₂, —NR¹³C(O)R¹³, —NO₂, and —SO₂R¹³; each R¹³ is independentlyhydrogen, optionally substituted C₁-C₆ (e.g., C₁-C₄) linear or branchedalkyl, optionally substituted C₁-C₆ (e.g., C₁-C₄) linear or branchedhaloalkyl, optionally substituted C₃-C₆ cycloalkyl (e.g., C₃-C₄cycloalkyl), optionally substituted aryl, optionally substitutedheterocycle, or optionally substituted heteroaryl, or two R¹³ units canbe taken together to form a ring comprising from 3-7 ring atoms. Whentwo R¹³ units are taken together to form a ring, the ring may compriseadditional heteroatoms independently selected from oxygen, nitrogen, orsulfur and may be optionally substituted. Non-limiting examples of twoR¹³ unit derived rings include piperidinyl, piperazinyl, morpholinyl,and pyrrolidinyl. In certain aspects, the substituents on the optionallysubstituted linear or branched alkyl group is a C₃-C₆ cycloalkyl. Thephenyl group can be substituted at any position on the ring, e.g., meta,para, and/or ortho positions.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is phenyl optionally substituted with —OCH₃ and —OCHF₂, forexample, 4-methoxyphenyl or 4-difluoro-methoxyphenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl,2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl,2,6-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl,2,3,4-trifluorophenyl, 2,3,5-trifluorophenyl, 2,3,6-trifluorophenyl,2,4,5-trifluorophenyl, 3,4,5-trifluorophenyl, 2,4,6-trifluorophenyl,2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl,2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl,3,4-dichlorophenyl, 2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl,2,3,6-trichlorophenyl, 2,4,5-trichlorophenyl, 3,4,5-trichlorophenyl, or2,4,6-trichlorophenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is phenyl optionally substituted with halogen substitutedalkoxy units, non-limiting examples of which include2-fluoromethoxyphenyl, 3-fluoromethoxyphenyl, 4-fluoromethoxyphenyl,2-difluoromethoxyphenyl, 3-difluoromethoxyphenyl,4-difluoromethoxyphenyl, 2-trifluoromethoxyphenyl,3-tri-fluoromethoxyphenyl, or 4-trifluoromethoxyphenyl

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl,2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl,2,3,4-trimethylphenyl, 2,3,5-trimethylphenyl, 2,3,6-trimethylphenyl,2,4,5-trimethylphenyl, 2,4,6-trimethylphenyl, 3,4,5-trimethylphenyl,2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2,3-diethylphenyl,2,4-diethylphenyl, 2,5-diethylphenyl, 2,6-diethylphenyl,3,4-diethylphenyl, 2,3,4-triethylphenyl, 2,3,5-triethylphenyl,2,3,6-triethylphenyl, 2,4,5-triethylphenyl, 3,4,5-triethylphenyl, or2,4,6-triethylphenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl,2,3-dimethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl,2,6-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl,2,3,4-trimethoxyphenyl, 2,3,5-trimethoxyphenyl, 2,3,6-trimethoxyphenyl,2,4,5-trimethoxyphenyl, 2,4,6-trimethoxyphenyl, 2-hydroxyphenyl,3-hydroxyphenyl, 4-hydroxyphenyl, 2,3-dihydroxyphenyl,2,4-dihydroxyphenyl, 2,5-dihydroxy-phenyl, 2,6-dihydroxyphenyl,3,4-dihydroxyphenyl, 2,3,4-trihydroxyphenyl, 2,3,5-trihydroxyphenyl,2,3,6-trihydroxyphenyl, 2,4,5-trihydroxyphenyl, 3,4,5-trihydroxyphenyl,or 2,4,6-trihydroxy-phenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl,2,3-dicyanophenyl, 2,4-dicyanophenyl, 2,5-dicyanophenyl,2,6-dicyanophenyl, 3,4-dicyanophenyl, 3,5-dicyanophenyl,2,3,4-tricyanophenyl, 2,3,5-tricyanophenyl, 2,3,6-tricyanophenyl,2,4,5-tricyanophenyl, 3,4,5-tricyanophenyl, or 2,4,6-tricyanophenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl,2,3-dinitrophenyl, 2,4-dinitrophenyl, 2,5-dinitrophenyl,2,6-dinitrophenyl, 3,4-dinitrophenyl, 3,5-dinitrophenyl,2,3,4-trinitrophenyl, 2,3,5-trinitrophenyl, 2,3,6-trinitrophenyl,2,4,5-trinitrophenyl, 3,4,5-trinitrophenyl, or 2,4,6-trinitrophenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is 2,6-dimethyl-4-fluorophenyl, 2,6-dimethyl-3-fluorophenyl,2,6-dimethyl-4-chlorophenyl, 2,6-di-tert-butyl-4-hydroxyphenyl,2,6-difluoro-4-chlorophenyl, 2,6-difluoro-3-chlorophenyl,2-hydroxy-4-methylphenyl, 2-hydroxy-5-methylphenyl,2,6-dihydroxy-4-tert-butylphenyl, or 2,6-difluoro-4-cyanophenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R is 3-dimethylaminophenyl, 4-dimethylaminophenyl,3-diethylaminophenyl, 4-diethylaminophenyl, 3-methylsulfanylphenyl,4-methylsulfanyl-phenyl, 3-ethylsulfanylphenyl, 4-ethylsulfanylphenyl,3-propylsulfanylphenyl, or 4-propylsulfanylphenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX) or a pharmaceutically acceptable salt form thereof,wherein R is 2-aminophenyl, 2-(N-methylamino)phenyl,2-(N,N-dimethylamino)phenyl, 2-(N-ethylamino)phenyl,2-(N,N-diethylamino)phenyl, 3-aminophenyl, 3-(N-methylamino)phenyl,3-(N,N-dimethylamino)phenyl, 3-(N-ethylamino)phenyl,3-(N,N-diethylamino)phenyl, 4-aminophenyl, 4-(N-methylamino)phenyl,4-(N,N-dimethylamino)phenyl, 4-(N-ethylamino)phenyl, or4-(N,N-diethylamino)phenyl.

In the present invention, R¹ is optionally substituted phenyl,optionally substituted C₁-C₆ linear or branched alkyl, optionallysubstituted C₃-C₇ cyclic alkyl, or optionally substituted heteroaryl.

In certain aspects, R¹ is optionally substituted phenyl. The phenylgroup can be substituted with any of the substituents provided herein.Examples of suitable substituents include, but are not limited tohalogen, optionally substituted C₁-C₆ linear or branched alkyl,optionally substituted C₁-C₆ linear or branched haloalkyl, optionallysubstituted C₃-C₆ cycloalkyl, —OR¹³, —CN, —N(R¹³)₂, —CO₂R¹³,—C(O)N(R¹³)₂, —NR¹³C(—O)R¹³, —NO₂, and —SO₂R¹³; each R¹³ isindependently hydrogen, optionally substituted C₁-C₆ (e.g., C₁-C₄)linear or branched alkyl, optionally substituted C₁-C₆ (e.g., C₁-C₄)linear or branched haloalkyl, optionally substituted C₃-C₆ cycloalkyl(e.g., C₃-C₄ cycloalkyl), optionally substituted aryl, optionallysubstituted heterocycle, or optionally substituted heteroaryl, or twoR¹³ units can be taken together to form a ring comprising from 3-7 ringatoms. When two R¹³ units are taken together to form a ring, the ringmay comprise additional heteroatoms independently selected from oxygen,nitrogen, or sulfur and may be optionally substituted. Non-limitingexamples of two R¹³ unit derived rings include piperidinyl, piperazinyl,morpholinyl, and pyrrolidinyl. In certain aspects, the substituent onthe optionally substituted linear or branched alkyl group is a C₃-C₆cycloalkyl. The phenyl group can be substituted at any position on thering, e.g., meta, para, and/or ortho positions.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R¹ is 4-methyl-phenyl, 4-fluorophenyl, 4-chlorophenyl,4-(fluoromethyl)phenyl, 4-(difluoromethoxy)-phenyl,4-(trifluoromethyl)phenyl, 4-methoxyphenyl, 3-methyl-4-methoxyphenyl,3-methoxy-4-methylphenyl, 3,4-di-methoxyphenyl, 3,4-dimethylphenyl,4-cyclopropyl-phenyl, 4-tert-butylphenyl, or 4-(2-methoxyethoxy)phenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R¹ is optionally substituted phenyl, 2-fluorophenyl,3-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl,2,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl,2,3,4-trifluorophenyl, 2,3,5-trifluorophenyl, 2,3,6-trifluorophenyl,2,4,5-trifluorophenyl, 2,4,6-trifluorophenyl, 2-chlorophenyl,3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl,2,5-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl,2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl, 2,3,6-trichlorophenyl,2,4,5-trichlorophenyl, 3,4,5-trichlorophenyl, or 2,4,6-trichlorophenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R¹ is 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl,2,6-dimethylphenyl, 3,4-dimethylphenyl, 2,3,4-trimethylphenyl,2,3,5-trimethylphenyl, 2,3,6-trimethylphenyl, 2,4,5-trimethylphenyl,2,4,6-trimethylphenyl, 2-ethylphenyl, 3-ethyl-phenyl, 4-ethylphenyl,2,3-diethylphenyl, 2,4-diethylphenyl, 2,5-diethylphenyl,2,6-diethylphenyl, 3,4-diethylphenyl, 2,3,4-triethylphenyl,2,3,5-triethylphenyl, 2,3,6-triethylphenyl, 2,4,5-triethylphenyl,2,4,6-triethylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, or4-isopropylphenyl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R¹ has the formula:

wherein R¹⁰ and R¹¹ or R¹¹ and R¹² are taken together with the atom towhich they are bound to form an optionally substituted ring having from5 to 7 ring atoms, optionally containing one or more hetoroatomsindependently selected from N, O, or S, Non-limiting examples of R¹ unitaccording to this aspect include benzo[1,3]-dioxol-4-yl,2-methylbenzo[1,3]dioxol-4-yl, 2,2-difluorobenzo[1,3]dioxol-4-yl,2-methylbenzo[1,3]dioxol-5-yl, 2,2-dimethylbenzo[1,3]dioxol-5-yl,2,2-difluorobenzo[1,3]-dioxol-5-yl,2-methyl-2,3-dihydrobenzo[1,4]-dioxin-5-yl,2-hydroxymethyl-2,3-dihydrobenzo[1,4]dioxin-5-yl,2,3-dihydro-benzo[1,4]dioxin-6-yl,2-methyl-2,3-dihydrobenzo[1,4]dioxin-6-yl, and2-hydroxymethyl-2,3-dihydrobenzo-[1,4]dioxin-6-yl.

Exemplary embodiments of the present invention include a compound ofFormulas (I)-(XIX), or a pharmaceutically acceptable salt form thereof,wherein R¹ is 2-aminophenyl, 2-(N-methylamino)phenyl,2-(N,N-dimethylamino)phenyl, 2-(N-ethylamino)phenyl,2-(N,N-diethylamino)phenyl, 3-aminophenyl, 3-(N-methylamino)phenyl,3-(N,N-dimethylamino)phenyl, 3-(N-ethylamino)phenyl,3-(N,N-diethylamino)phenyl, 4-aminophenyl, 4-(N-methylamino)phenyl,4-(N,N-dimethylamino)phenyl, 4-(N-ethylamino)phenyl, and4-(N,N-diethylamino)phenyl.

Compounds of the present invention include a compound of Formulas(I)-(XIX), or a pharmaceutically acceptable salt form thereof, whereinR¹ is butyl, cyclohexyl, quinolinyl, pyrrolidinyl, or6-methoxypyrridin-3-yl.

Compounds of the present invention include those wherein the substituenton the C₁-C₆ optionally substituted linear or branched alkyl of R^(8a)and R^(8b) is C₃-C₆ cycloalkyl.

Compounds of the present invention include those wherein R^(1a) ishydrogen.

Compounds of the present invention include those wherein the heteroarylof R⁴ is a C₁₋₁₀ heteroaryl and the heterocycle of R⁴ is a C₁₋₁₀heterocycle.

Compounds of the present invention include those wherein R² and R³ areboth hydrogen. Also included in the present invention are compoundswherein R² and R³ are not both hydrogen. Also included in the presentinvention are compounds wherein when one of R² and R³ is hydrogen oroptionally substituted alkyl, the other of R² and R³ is not hydrogen oroptionally substituted alkyl.

Compounds of the present invention include those wherein R² and R³ canbe taken together to form dioxidoisothiazolidinyl or piperazinyloptionally substituted with —C(O)NH₂, or —C(O)CH₃.

Compounds f of the present invention include those wherein theheteroaryl and heterocycle groups of the present invention areindependently selected from pyridinyl, furanyl, isoxazolyl, quinolinyl,imidazolyl, morpholinyl, piperidinyl, piperazinyl, or pyrazinyl.

Compounds of the present invention include those wherein R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ and j is 0 (i.e., R² is —SO₂R⁴) and R⁴ is—N(R^(6a)R^(6b)), optionally substituted C₁-C₆ linear or branched alkyl,or optionally substituted C₃-C₆ cycloalkyl. Non-limiting examples of R⁴include —NH₂, methyl, fluoromethyl, difluoromethyl, chloromethyl,dichloromethyl, trichloromethyl, ethyl, 2,2,2-trifluoroethyl,2,2,2-trichloroethyl, n-propyl, iso-propyl, cyclopropyl, n-butyl,iso-butyl, tert-butyl, and cyclobutyl.

Compounds of the present invention include those wherein R² isSO₂[C(R^(5a)R^(5b))]_(j)R⁴; wherein R⁴ is optionally substituted phenyl,C₄-C₅ optionally substituted heterocycle, or C₃-C₅ optionallysubstituted heteroaryl; and j is 0, 1, 2 or 3. Non-limiting examples ofR⁴ include phenyl, furan-2-yl, isoxazol-5-yl, imidazol-1-yl,pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazin-2-yl, piperidin-1-yl,4-methylpiperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, andmorpholin-4-yl. In certain embodiments, j is 1, 2, or 3. In someembodiments R^(5a) and R^(5b) are each hydrogen (i.e. R² is—SO₂(CH₂)_(j)R⁴).

Compounds of the present invention include those wherein R² is(piperidin-1-yl-ethyl)sulfonyl, (4-methylpiperidin-1-yl-ethyl)sulfonyl,(piperazin-1-yl-ethyl)sulfonyl, (4-methylpiperazin-1-yl-ethyl)sulfonyl,or (morpholin-4-yl-ethyl)sulfonyl.

Compounds of the present invention include those wherein R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ and j is 0 (i.e., R² is —SO₂R⁴) wherein R⁴is optionally substituted C₁-C₆ linear or branched alkyl, optionallysubstituted C₃-C₆ cycloalkyl, or optionally substituted C₂-C₆ linear orbranched alkenyl. Non-limiting examples of R⁴ include methyl, ethyl,n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl,fluoromethyl, chloromethyl, cyanomethyl, trifluoromethyl, CH₂CF₃,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and alkenyl. Compoundsof the present invention include those wherein R² is methanesulfonyl.

Compounds of the present invention include those wherein R² ismethanesulfonyl and R³ is hydrogen.

Compounds of the present invention include those wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴ and k is 0 (i.e., R² is —C(O)R⁴) and R⁴ isoptionally substituted C₁-C₆ linear or branched alkyl or optionallysubstituted C₃-C₆ cycloalkyl. Non-limiting examples of R⁴ includemethyl, fluoromethyl, difluoromethyl, trifluoromethyl,(N-methyl-N-benzyl)aminomethyl,(N-methyl-N-tert-butoxycarbonyl)aminomethyl, ethyl,2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, n-propyl, iso-propyl,cyclopropyl, n-butyl, iso-butyl, tert-butyl, cyclopropylmethyl, andcyclobutyl.

Compounds of the present invention include those wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴ and R⁴ is optionally substituted phenyl ornaphthyl. In some embodiments R^(5a) and R^(5b) are each hydrogen (i.e.R² is —C(O)(CH₂)_(k)R⁴). Non-limiting examples of R⁴ include phenyl,4-fluoro-phenyl, 4-chlorophenyl, 4-(trifluoromethyl)phenyl,4-methoxyphenyl, and 4-(trifluoromethoxy)phenyl.

Compounds of the present invention include those wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴; R⁴ is optionally substituted C₁-C₁₀heteroaryl, or optionally substituted C₁-C₁₀ heterocycle; and k is 0 to2. In some embodiments R^(5a) and R^(5b) are each hydrogen (i.e. R² is—C(O)(CH₂)_(k)R⁴). Non-limiting examples of R⁴ include furan-2-yl,isoxazol-5-yl, imidazol-1-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,pyrazin-2-yl, piperidin-1-yl, 4-methylpiperidin-1-yl, piperazin-1-yl,4-methylpiperazin-1-yl, and morpholin-4-yl.

Compounds of the present invention include those wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴; R⁴ is optionally substituted methoxy,optionally substituted ethoxy, optionally substituted n-propoxy,optionally substituted iso-propoxy, optionally substituted n-butoxy,optionally substituted iso-butoxy, or optionally substitutedtert-butoxy; and k is 1 or 2. In some embodiments R^(5a) and R^(5b) areeach hydrogen (i.e. R² is —C(O)(CH₂)_(k)R⁴).

Compounds of the present invention include those wherein R² is—[C(R^(5a)R^(5b))]_(n)R⁴; R⁴ is optionally substituted aryl, optionallysubstituted aryloxy, optionally substituted C₃-C₉ heterocycle, oroptionally substituted C₃-C₉ heteroaryl; and n is 1 or 2. In someembodiments R^(5a) and R^(5b) are each hydrogen (i.e. R² is—(CH₂)_(n)R⁴). Non-limiting examples of R⁴ include phenyl,quinolin-2-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,4-dimethylaminophenyl, 4-diethylaminophenyl, 4-fluorophenyl,4-chlorophenyl, 4-(imidazol-1-yl)phenyl, and 4-cyanophenyl.

Compounds of the present invention include those wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)N(R^(6a)R^(6b)) wherein R^(6b) is hydrogen ormethyl; R^(6b) is —C(O)OR^(7a); and R^(7a) is methyl, ethyl, ortert-butyl. Non-limiting examples of R² include —C(O)CH₂NHC(O)OC(CH₃)₃,—C(O)CH₂N(CH₃)C(O)OC(CH₃)₃ and —C(O)CH₂N(CH₃)C(O)OCH₃.

Compounds of the present invention include those wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)N(R^(6a)R^(6b)) wherein R^(6b) is hydrogen ormethyl, and R^(6a) is optionally substituted benzyl.

Compounds of the present invention include those wherein R² is C(O)CH₃,C(O)OCH₃, —C(O)cyclopropyl, C(O)OC(CH₃)₃, C(O)CH₂N(CH₃)benzyl,C(O)CH₂N(CH₃)C(O)OR^(7a), —C(O)furan-2-yl, C(O)C₆H₅, C(O)CH₂C₆H₅,C(O)CH₂OC₆H₅, —C(O)isoxazol-5-yl, —C(O)pyrazin-2-yl, —CH₂(cyclopropyl),CH₂C₆H₅, CH₂CH₂C₆H₅, CH₂C₆H₄(4-CN), CH₂C₆H₄(4-F),—CH₂C₆H_(4[)4-N(CH₃)₂], —CH₂C₆H_(4[)4-N(C₂H₅)₂],—CH₂C₆H_(4[)4-imidazolyl], —CH₂(imidazol-1-yl), —CH₂(pyridine-2-yl),CH₂(pyridine-3-yl), or CH₂(pyridine-4-yl) and R^(7a) is tert-butyl.

Compounds of the present invention include those wherein R² is SO₂R₄,SO₂CH₂C(O)N(R^(8a)R^(8b)), SO₂[C(R^(5a)R^(5b))]_(j)SO₂—R⁷, orSO₂[C(R^(5a)R^(5b))]_(j)R⁴

Compounds of the present invention include those wherein R³ is hydrogen,optionally substituted C₁-C₄ linear or branched alkyl, or optionallysubstituted C₃-C₄ cycloalkyl. Non-limiting examples include methyl,ethyl, n-propyl, isopropyl, and cyclopropyl.

Compounds of the present invention include those wherein R² is hydrogen,SO₂R₄, SO₂CH₂C(O)N(R^(8a)R^(8b)), SO₂[C(R^(5a)R^(5b))]_(j)SO₂—R⁷, orSO₂[C(R^(5a)R^(5b))]_(j)R⁴; R⁴ is —NH₂, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃,—CH₂CH₂CH₂CH₂, —CH₂F, —CH₂Cl, —CCl₃, —CH₂CH₂F, —CH₂CHF₂, —CH₂CF₃,-cyclopropyl, —CH═CH₂, CHF₂, CHCl₂, —CH₂CN, -(pyridin-2-yl),-(pyridin-3-yl), -(pyridin-4-yl), or —C₆H₅; R^(8a) is hydrogen, —CH₃,-cyclopropyl, or —CH₂(cyclopropyl); R^(8b) is hydrogen, —CH₃,-cyclopropyl, or —CH₂(cyclopropyl); R^(5a) is hydrogen; R^(5b) ishydrogen; R⁷ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, or-cyclopropyl, and j is 0, 1 or 2

Compounds of the present invention include those wherein when R² or R³is —[C(R^(5a)R^(5b))]_(n)R⁴, then R⁴ is not aryloxy.

Compounds of the present invention include those wherein R² and R³ aretaken together form an optionally substituted ring having from 3 to 7ring atoms, then R is phenyl optionally substituted by at least onealkoxy substituent.

Compounds of the present invention include those wherein j is zero.

Compounds of the present invention include those wherein j is from 1 to4.

Compounds of the present invention include those wherein when R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴, wherein R⁴ is optionally substitutedlinear or branched alkoxy, then R³ is not —[C(R^(5a)R^(5b))]_(n)R⁴wherein R⁴ is optionally substituted quinolinyl.

Compounds of the present invention include those wherein when R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴ wherein R⁴ is optionally substituted linearor branched alkoxy, then R³ is not —[C(R^(5a)R^(5b))]_(n)R⁴ wherein R⁴is optionally substituted heteroaryl.

Compounds of the present invention include those wherein when R³ ishydrogen, then R² is not —C(O)[C(R^(5a)R^(5b))]_(k)R⁴ wherein R⁴ isoptionally substituted aryloxy.

Compounds of the present invention include those wherein when R³ ishydrogen, then R² is not —SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is—N(R^(6a)R^(6b)) and one of R^(6a) and R^(6b) is hydrogen and the otheris —C(O)OR^(7a) when R^(7a) is optionally substituted linear or branchedalkyl.

Compounds of the present invention include those wherein when R² and R³are hydrogen, then R is substituted phenyl.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is phenyl or naphthyl, then R³ isnot SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is phenyl or naphthyl.

Compounds of the present invention include those wherein when R³ is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴ wherein R⁴ is phenyl or naphthyl, then R²is not hydrogen.

Compounds of the present invention include those wherein when R³ is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴ wherein R⁴ is —N(R^(6a)R^(6b)) and one ofR^(6a) and R^(6b) is hydrogen and the other is phenyl, then R² is nothydrogen.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is hydrogen or linear or branchedalkyl, then R³ is not —[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is optionallysubstituted imidazolyl.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is hydrogen or linear or branchedalkyl, then R³ is not —[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is optionallysubstituted heteroaryl.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is pyridinyl, then R³ is nothydrogen.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is optionally substitutedheteroaryl, then R³ is not hydrogen.

Compounds of the present invention include those wherein when R² isC(O)[C(R^(5a)R^(5b))]_(k)R⁴ wherein R⁴ is hydrogen or linear or branchedalkyl, then R³ is not hydrogen.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is C(O)NR^(8a)R^(8b) andR^(8a)R^(8b) form a piperazinyl ring substituted with acetyl, then R³ isnot hydrogen.

Compounds of the present invention include those wherein when R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ wherein R⁴ is C(O)NR^(8a)R^(8b) andR^(8a)R^(8b) form a ring having from 3 to 7 ring atoms, then R³ is nothydrogen.

In all of the embodiments provided herein, examples of suitable optionalsubstituents are not intended to limit the scope of the claimedinvention. The compounds of the invention may contain any of thesubstituents, or combinations of substituents, provided herein.

Compounds of the present invention include those wherein R⁷ is hydrogen,optionally substituted C₁-C₆ linear or branched alkyl, optionallysubstituted C₃-C₆ cycloalkyl, NH₂, —NH(C₁-C₄ alkyl), or —N(C₁-C₄alkyl)₂.

Compounds of the present invention include those wherein R^(9a) andR^(9b) are, at each occurrence, each independently hydrogen or methyl,or when m is 1, R^(9a) and R^(9b) can be taken together with the atom towhich they are bound to form a cyclopropyl ring.

Compounds of the present invention include those wherein L and L¹ are,independently, —[C(R^(9a)R^(9b))]_(m)— and R^(9a) and R^(9b) are at eachoccurrence, each independently hydrogen or methyl, or R^(9a) and R^(9b)can be taken together to form a cyclopropyl ring.

In some embodiments, y is 0 (i.e., L¹ is absent). In other embodiments,y is 1 and L¹ is —CH₂—. In still other embodiments, y is 1 and L¹ is:

In certain aspects, L is —[C(R^(9a)R^(9b))]_(m)— wherein R^(9a) andR^(9b) are, at each occurrence, each independently hydrogen or methyl; xis 0 or 1; and m is 0 to 4. When x is equal to 0, linking group L isabsent, when x is equal to 1, linking group L is present.

Compounds of the present invention include those wherein L is —CH₂CH₂—(ethylene) (i.e., R^(9a) and R^(9b) are each a hydrogen and m is 2).

Compounds of the present invention include compounds having Formulas IIIor IV, or a pharmaceutically acceptable salt form thereof:

wherein R, R¹, R^(1a), R², and R³ are the same as defined herein.

Compounds of the present invention include those wherein L is—CH₂-(methylene) (i.e., R^(9a) and R^(9b) are each a hydrogen and m is1).

Compounds of the present invention include those having Formulas V or VIor a pharmaceutically acceptable salt form thereof:

wherein R, R¹, R^(1a), R², and R³ are the same as defined herein.

Compounds of the present invention include those wherein L is—CH₂CH₂CH₂— (propylene) (i.e., R^(9a) and R^(9b) are each a hydrogen andm is 3).

Compounds of the present invention include compounds having Formulas VIIor VIII or a pharmaceutically acceptable salt form thereof:

wherein R, R¹, R^(1a), R², and R³ are the same as defined herein.

Compounds of the present invention include compounds having Formula IX,or a pharmaceutically acceptable salt form thereof:

wherein R² and R³ are each hydrogen and non-limiting examples of R, R¹and L are described in Table I and the examples herein below. TABLE I RR¹ L 4-methoxyphenyl 4-tert-butylphenyl —CH₂CH₂— 4-methoxyphenyl4-cyclopropylphenyl —CH₂CH₂— 4-methoxyphenyl 3,4-dimethylphenyl —CH₂CH₂—4-methoxyphenyl 4-methoxyphenyl —CH₂CH₂— 4-methoxyphenyl4-difluoromethoxyphenyl —CH₂CH₂— 4-methoxyphenyl 4-isopropoxyphenyl—CH₂CH₂— 4-methoxyphenyl 4-(diethylamino)phenyl —CH₂CH₂— 4-methoxyphenylbenzo[1,3]dioxol-5-yl —CH₂CH₂— 4-methoxyphenyl2,2-difluorobenzo[1,3]-dioxol-5-yl —CH₂CH₂— 4-methoxyphenyl2,2-dimethylbenzo[1,3]dioxol-5-yl —CH₂CH₂— 4-methoxyphenyl2,3-dihydro-benzo[1,4]dioxin-6-yl —CH₂CH₂— phenyl 4-tert-butylphenyl—CH₂CH₂CH₂— phenyl 4-cyclopropylphenyl —CH₂CH₂CH₂— phenyl3,4-dimethylphenyl —CH₂CH₂CH₂— phenyl 4-methoxyphenyl —CH₂CH₂CH₂— phenyl4-difluoromethoxyphenyl —CH₂CH₂CH₂— phenyl 4-isopropoxyphenyl—CH₂CH₂CH₂— phenyl 4-(diethylamino)phenyl —CH₂CH₂CH₂— phenylbenzo[1,3]dioxol-5-yl —CH₂CH₂CH₂— phenyl2,2-difluorobenzo[1,3]-dioxol-5-yl —CH₂CH₂CH₂— phenyl2,2-dimethylbenzo[1,3]dioxol-5-yl —CH₂CH₂CH₂— phenyl2,3-dihydro-benzo[1,4]dioxin-6-yl —CH₂CH₂CH₂—

Compounds of the present invention include compounds having formula X,or a pharmaceutically acceptable salt form thereof:

Compounds of the present invention include compounds having Formula XI,or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, and R⁴ are defined herein belowin Table II. TABLE II R R¹ R⁴ 4-methoxyphenyl 3,4-dimethylphenyl —NH₂4-methoxyphenyl 3,4-dimethylphenyl —CH₃ 4-methoxyphenyl3,4-dimethylphenyl —CH₂CH₃ 4-methoxyphenyl 3,4-dimethylphenyl —CH₂CH₂CH₃4-methoxyphenyl 3,4-dimethylphenyl —CH₂CH₂CH₂CH₃ 4-methoxyphenyl3,4-dimethylphenyl —CH₂F 4-methoxyphenyl 3,4-dimethylphenyl —CHF₂4-methoxyphenyl 3,4-dimethylphenyl —CH₂Cl 4-methoxyphenyl3,4-dimethylphenyl —CHCl₂ 4-methoxyphenyl 3,4-dimethylphenyl —CCl₃4-methoxyphenyl 3,4-dimethylphenyl —CH₂CH₂F 4-methoxyphenyl3,4-dimethylphenyl —CH₂CHF₂ 4-methoxyphenyl 3,4-dimethylphenyl —CH₂CF₃4-methoxyphenyl 3,4-dimethylphenyl -cyclopropyl 4-methoxyphenyl3,4-dimethylphenyl —CH═CH₂ 4-methoxyphenyl 4-tert-butylphenyl —NH₂4-methoxyphenyl 4-tert-butylphenyl —CH₃ 4-methoxyphenyl4-tert-butylphenyl —CH₂CH₃ 4-methoxyphenyl 4-tert-butylphenyl —CH₂CH₂CH₃4-methoxyphenyl 4-tert-butylphenyl —CH₂CH₂CH₂CH₃ 4-methoxyphenyl4-tert-butylphenyl —CH₂F 4-methoxyphenyl 4-tert-butylphenyl —CHF₂4-methoxyphenyl 4-tert-butylphenyl —CH₂Cl 4-methoxyphenyl4-tert-butylphenyl —CHCl₂ 4-methoxyphenyl 4-tert-butylphenyl —CCl₃4-methoxyphenyl 4-tert-butylphenyl —CH₂CH₂F 4-methoxyphenyl4-tert-butylphenyl —CH₂CHF₂ 4-methoxyphenyl 4-tert-butylphenyl —CH₂CF₃4-methoxyphenyl 4-tert-butylphenyl -cyclopropyl 4-methoxyphenyl4-tert-butylphenyl —CH═CH₂ 4-methoxyphenyl 4-cyclopropylphenyl —NH₂4-methoxyphenyl 4-cyclopropylphenyl —CH₃ 4-methoxyphenyl4-cyclopropylphenyl —CH₂CH₃ 4-methoxyphenyl 4-cyclopropylphenyl—CH₂CH₂CH₃ 4-methoxyphenyl 4-cyclopropylphenyl —CH₂CH₂CH₂CH₃4-methoxyphenyl 4-cyclopropylphenyl —CH₂F 4-methoxyphenyl4-cyclopropylphenyl —CHF₂ 4-methoxyphenyl 4-cyclopropylphenyl —CH₂Cl4-methoxyphenyl 4-cyclopropylphenyl —CHCl₂ 4-methoxyphenyl4-cyclopropylphenyl —CCl₃ 4-methoxyphenyl 4-cyclopropylphenyl —CH₂CH₂F4-methoxyphenyl 4-cyclopropylphenyl —CH₂CHF₂ 4-methoxyphenyl4-cyclopropylphenyl —CH₂CF₃ 4-methoxyphenyl 4-cyclopropylphenyl-cyclopropyl 4-methoxyphenyl 4-cyclopropylphenyl —CH═CH₂ 4-methoxyphenyl4-methoxyphenyl —NH₂ 4-methoxyphenyl 4-methoxyphenyl —CH₃4-methoxyphenyl 4-methoxyphenyl —CH₂CH₃ 4-methoxyphenyl 4-methoxyphenyl—CH₂CH₂CH₃ 4-methoxyphenyl 4-methoxyphenyl —CH₂CH₂CH₂CH₃ 4-methoxyphenyl4-methoxyphenyl —CH₂F 4-methoxyphenyl 4-methoxyphenyl —CHF₂4-methoxyphenyl 4-methoxyphenyl —CH₂Cl 4-methoxyphenyl 4-methoxyphenyl—CHCl₂ 4-methoxyphenyl 4-methoxyphenyl —CCl₃ 4-methoxyphenyl4-methoxyphenyl —CH₂CH₂F 4-methoxyphenyl 4-methoxyphenyl —CH₂CHF₂4-methoxyphenyl 4-methoxyphenyl —CH₂CF₃ 4-methoxyphenyl 4-methoxyphenyl-cyclopropyl 4-methoxyphenyl 4-methoxyphenyl —CH═CH₂

Compounds of the present invention include compounds having Formula XII,or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, R⁴, and L are defined hereinbelow in Table III. TABLE III R L R¹ R⁴ phenyl —CH₂CH₂CH₂—4-tert-butylphenyl —NH₂ phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CH₃phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CH₂CH₃ phenyl —CH₂CH₂CH₂—4-tert-butylphenyl —CH₂CH₂CH₃ phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl—CH₂CH₂CH₂CH₃ phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CH₂F phenyl—CH₂CH₂CH₂— 4-tert-butylphenyl —CHF₂ phenyl —CH₂CH₂CH₂—4-tert-butylphenyl —CH₂Cl phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CHCl₂phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CCl₃ phenyl —CH₂CH₂CH₂—4-tert-butylphenyl —CH₂CN phenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CH₂CH₂Fphenyl —CH₂CH₂CH₂— 4-tert-butylphenyl —CH₂CHF₂ phenyl —CH₂CH₂CH₂—4-tert-butylphenyl —CH₂CF₃ 4- —CH₂CH(CH₃)— 4-tert-butylphenyl —NH₂methoxy- phenyl 4- —CH₂CH(CH₃)— 4-tert-butylphenyl —CH₃ methoxy- phenyl4- —CH₂CH(CH₃)— 4-tert-butylphenyl —CH₂CH₃ methoxy- phenyl 4-—CH₂CH(CH₃)— 4-tert-butylphenyl —CH₂CH₂CH₃ methoxy- phenyl 4-—CH₂CH(CH₃)— 4-tert-butylphenyl —CH₂CH₂CH₂CH₃ methoxy- phenyl 4-—CH₂CH(CH₃)— 4-tert-butylphenyl —CH₂F methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CHF₂ methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CF₃ methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CH₂Cl methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CHCl₂ methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CCl₃ methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CH₂CN methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CH₂CH₂F methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CH₂CHF₂ methoxy- phenyl 4- —CH₂CH(CH₃)—4-tert-butylphenyl —CH₂CF₃ methoxy- phenyl

Compounds of the present invention include compounds having FormulaXIII, or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, and R⁴ are defined herein belowin Table IV. TABLE IV R R¹ N(R^(8a)R^(8b)) 4-methoxyphenyl4-tert-butylphenyl —NH₂ 4-methoxyphenyl 4-cyclopropylphenyl —NH₂4-methoxyphenyl 3,4-dimethylphenyl —NH₂ 4-methoxyphenyl 4-methoxyphenyl—NH₂ 4-methoxyphenyl 4-difluoromethylphenyl —NH₂ 4-methoxyphenyl4-isopropoxyphenyl —NH₂ 4-methoxyphenyl 4-(diethylamino)phenyl —NH₂4-methoxyphenyl benzo[1,3]dioxol-5-yl —NH₂ 4-methoxyphenyl 2,2- —NH₂difluorobenzo[1,3]-dioxol- 5-yl 4-methoxyphenyl 2,2- —NH₂dimethylbenzo[1,3]dioxol- 5-yl 4-methoxyphenyl 2,3- —NH₂dihydro-benzo[1,4]dioxin- 6-yl phenyl 4-tert-butylphenyl —NHCH₃ phenyl4-cyclopropylphenyl —NHCH₃ phenyl 3,4-dimethylphenyl —NHCH₃ phenyl4-methoxyphenyl —NHCH₃ phenyl 4-difluoromethylphenyl —NHCH₃ phenyl4-isopropoxyphenyl —NHCH₃ phenyl 4-(diethylamino)phenyl —NHCH₃ phenylbenzo[1,3]dioxol-5-yl —NHCH₃ phenyl 2,2- —NHCH₃difluorobenzo[1,3]-dioxol- 5-yl phenyl 2,2- —NHCH₃dimethylbenzo[1,3]dioxol- 5-yl phenyl 2,3- —NHCH₃dihydro-benzo[1,4]dioxin- 6-yl 4-methoxyphenyl 4-tert-butylphenyl—N(CH₃)₂ 4-methoxyphenyl 4-cyclopropylphenyl —N(CH₃)₂ 4-methoxyphenyl3,4-dimethylphenyl —N(CH₃)₂ 4-methoxyphenyl 4-methoxyphenyl —N(CH₃)₂4-methoxyphenyl 4-difluoromethylphenyl —N(CH₃)₂ 4-methoxyphenyl4-isopropoxyphenyl —N(CH₃)₂ 4-methoxyphenyl 4-(diethylamino)phenyl—N(CH₃)₂ 4-methoxyphenyl benzo[1,3]dioxol-5-yl —N(CH₃)₂ 4-methoxyphenyl2,2- —N(CH₃)₂ difluorobenzo[1,3]-dioxol- 5-yl 4-methoxyphenyl 2,2-—N(CH₃)₂ dimethylbenzo[1,3]dioxol- 5-yl 4-methoxyphenyl 2,3- —N(CH₃)₂dihydro-benzo[1,4]dioxin- 6-yl 4-methoxyphenyl 4-tert-butylphenyl—NH(cyclopropyl) 4-methoxyphenyl 4-cyclopropylphenyl —NH(cyclopropyl)4-methoxyphenyl 3,4-dimethylphenyl —NH(cyclopropyl) 4-methoxyphenyl4-methoxyphenyl —NH(cyclopropyl) 4-methoxyphenyl 4-difluoromethylphenyl—NH(cyclopropyl) 4-methoxyphenyl 4-isopropoxyphenyl —NH(cyclopropyl)4-methoxyphenyl 4-(diethylamino)phenyl —NH(cyclopropyl) 4-methoxyphenylbenzo[1,3]dioxol-5-yl —NH(cyclopropyl) 4-methoxyphenyl 2,2-—NH(cyclopropyl) difluorobenzo[1,3]-dioxol- 5-yl 4-methoxyphenyl 2,2-—NH(cyclopropyl) dimethylbenzo[1,3]dioxol- 5-yl 4-methoxyphenyl 2,3-—NH(cyclopropyl) dihydro-benzo[1,4]dioxin- 6-yl 4-methoxyphenyl4-tert-butylphenyl —NHCH₂(cyclopropyl) 4-methoxyphenyl4-cyclopropylphenyl —NHCH₂(cyclopropyl) 4-methoxyphenyl3,4-dimethylphenyl —NHCH₂(cyclopropyl) 4-methoxyphenyl 4-methoxyphenyl—NHCH₂(cyclopropyl) 4-methoxyphenyl 4-difluoromethylphenyl—NHCH₂(cyclopropyl) 4-methoxyphenyl 4-isopropoxyphenyl—NHCH₂(cyclopropyl) 4-methoxyphenyl 4-(diethylamino)phenyl—NHCH₂(cyclopropyl) 4-methoxyphenyl benzo[1,3]dioxol-5-yl—NHCH₂(cyclopropyl) 4-methoxyphenyl 2,2- —NHCH₂(cyclopropyl)difluorobenzo[1,3]-dioxol- 5-yl 4-methoxyphenyl 2,2- —NHCH₂(cyclopropyl)dimethylbenzo[1,3]dioxol- 5-yl 4-methoxyphenyl 2,3- —NHCH₂(cyclopropyl)dihydro-benzo[1,4]dioxin- 6-yl

Compounds of the present invention include compounds having Formula XIV,or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, R^(5a), R^(5b), and R⁷ aredefined herein below in Table V. TABLE V R R¹ C(R^(5a)R^(5b))_(j) R⁷4-methoxy- 3,4-dimethylphenyl —CH₂— —CH₃ phenyl 4-methoxy-3,4-dimethylphenyl —CH₂— —CH₂CH₃ phenyl 4-methoxy- 3,4-dimethylphenyl—CH₂— —CH₂CH₂CH₃ phenyl 4-methoxy- 3,4-dimethylphenyl —CH₂——CH₂CH₂CH₂CH₃ phenyl 4-methoxy- 3,4-dimethylphenyl —CH₂CH₂— —CH₃ phenyl4-methoxy- 3,4-dimethylphenyl —CH₂CH₂— —CH₂CH₃ phenyl 4-methoxy-3,4-dimethylphenyl —CH₂CH₂— —CH₂CH₂CH₃ phenyl 4-methoxy-3,4-dimethylphenyl —CH₂CH₂— —CH₂CH₂CH₂CH₃ phenyl 4-methoxy-4-tert-butylphenyl —CH₂— —CH₃ phenyl 4-methoxy- 4-tert-butylphenyl —CH₂——CH₂CH₃ phenyl 4-methoxy- 4-tert-butylphenyl —CH₂— —CH₂CH₂CH₃ phenyl4-methoxy- 4-tert-butylphenyl —CH₂— —CH₂CH₂CH₂CH₃ phenyl 4-methoxy-4-tert-butylphenyl —CH₂CH₂— —CH₃ phenyl 4-methoxy- 4-tert-butylphenyl—CH₂CH₂— —CH₂CH₃ phenyl 4-methoxy- 4-tert-butylphenyl —CH₂CH₂——CH₂CH₂CH₃ phenyl 4-methoxy- 4-tert-butylphenyl —CH₂CH₂— —CH₂CH₂CH₂CH₃phenyl 4-methoxy- 4-cyclopropylphenyl —CH₂— —CH₃ phenyl 4-methoxy-4-cyclopropylphenyl —CH₂— —CH₂CH₃ phenyl 4-methoxy- 4-cyclopropylphenyl—CH₂— —CH₂CH₂CH₃ phenyl 4-methoxy- 4-cyclopropylphenyl —CH₂——CH₂CH₂CH₂CH₃ phenyl 4-methoxy- 4-cyclopropylphenyl —CH₂CH₂— —CH₃ phenyl4-methoxy- 4-cyclopropylphenyl —CH₂CH₂— —CH₂CH₃ phenyl 4-methoxy-4-cyclopropylphenyl —CH₂CH₂— —CH₂CH₂CH₃ phenyl 4-methoxy-4-cyclopropylphenyl —CH₂CH₂— —CH₂CH₂CH₂CH₃ phenyl 4-methoxy-4-methoxyphenyl —CH₂— —CH₃ phenyl 4-methoxy- 4-methoxyphenyl —CH₂——CH₂CH₃ phenyl 4-methoxy- 4-methoxyphenyl —CH₂— —CH₂CH₂CH₃ phenyl4-methoxy- 4-methoxyphenyl —CH₂— —CH₂CH₂CH₂CH₃ phenyl 4-methoxy-4-methoxyphenyl —CH₂CH₂— —CH₃ phenyl 4-methoxy- 4-methoxyphenyl —CH₂CH₂——CH₂CH₃ phenyl 4-methoxy- 4-methoxyphenyl —CH₂CH₂— —CH₂CH₂CH₃ phenyl4-methoxy- 4-methoxyphenyl —CH₂CH₂— —CH₂CH₂CH₂CH₃ phenyl

Compounds of the present invention include compounds having Formula XV,or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, R^(5a), R^(5b), and R⁴ aredefined herein below in Table VI. TABLE VI R R¹ C(R^(5a)R^(5b))_(j) R⁴4-methoxyphenyl 3,4-dimethylphenyl — -(pyridin-2-yl) 4-methoxyphenyl3,4-dimethylphenyl — -(pyridin-3-yl) 4-methoxyphenyl 3,4-dimethylphenyl— -(pyridin-4-yl) 4-methoxyphenyl 3,4-dimethylphenyl — —C₆H₅4-methoxyphenyl 3,4-dimethylphenyl —CH₂— -(pyridin-2-yl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂— -(pyridin-3-yl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂— -(pyridin-4-yl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂— —C₆H₅ 4-methoxyphenyl 4-tert-butylphenyl —-(pyridin-2-yl) 4-methoxyphenyl 4-tert-butylphenyl — -(pyridin-3-yl)4-methoxyphenyl 4-tert-butylphenyl — -(pyridin-4-yl) 4-methoxyphenyl4-tert-butylphenyl — —C₆H₅ 4-methoxyphenyl 4-tert-butylphenyl —CH₂—-(pyridin-2-yl) 4-methoxyphenyl 4-tert-butylphenyl —CH₂— -(pyridin-3-yl)4-methoxyphenyl 4-tert-butylphenyl —CH₂— -(pyridin-4-yl) 4-methoxyphenyl4-tert-butylphenyl —CH₂— —C₆H₅ 4-methoxyphenyl 4-cyclopropylphenyl —-(pyridin-2-yl) 4-methoxyphenyl 4-cyclopropylphenyl — -(pyridin-3-yl)4-methoxyphenyl 4-cyclopropylphenyl — -(pyridin-4-yl) 4-methoxyphenyl4-cyclopropylphenyl — —C₆H₅ 4-methoxyphenyl 4-cyclopropylphenyl —CH₂—-(pyridin-2-yl) 4-methoxyphenyl 4-cyclopropylphenyl —CH₂—-(pyridin-3-yl) 4-methoxyphenyl 4-cyclopropylphenyl —CH₂—-(pyridin-4-yl) 4-methoxyphenyl 4-cyclopropylphenyl —CH₂— —C₆H₅4-methoxyphenyl 4-methoxyphenyl — -(pyridin-2-yl) 4-methoxyphenyl4-methoxyphenyl — -(pyridin-3-yl) 4-methoxyphenyl 4-methoxyphenyl —-(pyridin-4-yl) 4-methoxyphenyl 4-methoxyphenyl — —C₆H₅ 4-methoxyphenyl4-methoxyphenyl —CH₂— -(pyridin-2-yl) 4-methoxyphenyl 4-methoxyphenyl—CH₂— -(pyridin-3-yl) 4-methoxyphenyl 4-methoxyphenyl —CH₂—-(pyridin-4-yl) 4-methoxyphenyl 4-methoxyphenyl —CH₂— —C₆H₅

Compounds of the present invention include compounds having Formula XVI,or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, R^(5a), R^(5b), and R⁷ aredefined herein below in Table VII. TABLE VII R R¹ R³ C(R^(5a)R^(5b))_(j)R⁷ 4- 3,4-dimethylphenyl —CH₃ —CH₂— —CH₃ methoxy- phenyl 4-3,4-dimethylphenyl —CH₃ —CH₂— —CH₂CH₃ methoxy- phenyl 4-3,4-dimethylphenyl —CH₃ —CH₂— -cyclopropyl methoxy- phenyl 4-3,4-dimethylphenyl —CH₃ —CH₂CH₂— —CH₃ methoxy- phenyl 4-3,4-dimethylphenyl —CH₃ —CH₂CH₂— —CH₂CH₃ methoxy- phenyl 4-3,4-dimethylphenyl —CH₃ —CH₂CH₂— -cyclopropyl methoxy- phenyl 4-4-tert-butylphenyl —CH₃ —CH₂— —CH₃ methoxy- phenyl 4- 4-tert-butylphenyl—CH₃ —CH₂— —CH₂CH₃ methoxy- phenyl 4- 4-tert-butylphenyl —CH₃ —CH₂—-cyclopropyl methoxy- phenyl 4- 4-tert-butylphenyl —CH₃ —CH₂CH₂— —CH₃methoxy- phenyl 4- 4-tert-butylphenyl —CH₃ —CH₂CH₂— —CH₂CH₃ methoxy-phenyl 4- 4-tert-butylphenyl —CH₃ —CH₂CH₂— -cyclopropyl methoxy- phenyl4- 4-cyclopropylphenyl —CH₃ —CH₂— —CH₃ methoxy- phenyl 4-4-cyclopropylphenyl —CH₃ —CH₂— —CH₂CH₃ methoxy- phenyl 4-4-cyclopropylphenyl —CH₃ —CH₂— -cyclopropyl methoxy- phenyl 4-4-cyclopropylphenyl —CH₃ —CH₂CH₂— —CH₃ methoxy- phenyl 4-4-cyclopropylphenyl —CH₃ —CH₂CH₂— —CH₂CH₃ methoxy- phenyl 4-4-cyclopropylphenyl —CH₃ —CH₂CH₂— -cyclopropyl methoxy- phenyl 4-4-methoxyphenyl —CH₃ —CH₂— —CH₃ methoxy- phenyl 4- 4-methoxyphenyl —CH₃—CH₂— —CH₂CH₃ methoxy- phenyl 4- 4-methoxyphenyl —CH₃ —CH₂— -cyclopropylmethoxy- phenyl 4- 4-methoxyphenyl —CH₃ —CH₂CH₂— —CH₃ methoxy- phenyl 4-4-methoxyphenyl —CH₃ —CH₂CH₂— —CH₂CH₃ methoxy- phenyl 4- 4-methoxyphenyl—CH₃ —CH₂CH₂— -cyclopropyl methoxy- phenyl

Compounds of the present invention include compounds having FormulaXVII, or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, and R² are defined herein belowin Table VIII. TABLE VIII R R¹ R² 4-methoxyphenyl 3,4-dimethylphenyl—C(O)CH₃ 4-methoxyphenyl 3,4-dimethylphenyl —C(O)OCH₃ 4-methoxyphenyl3,4-dimethylphenyl —C(O)(cyclopropyl) 4-methoxyphenyl 3,4-dimethylphenyl—C(O)OC(CH₃)₃ 4-methoxyphenyl 3,4-dimethylphenyl —C(O)CH₂N(CH₃)benzyl4-methoxyphenyl 3,4-dimethylphenyl —C(O)CH₂N(CH₃)Boc 4-methoxyphenyl3,4-dimethylphenyl —C(O)furan-2-yl 4-methoxyphenyl 3,4-dimethylphenyl—C(O)C₆H₅ 4-methoxyphenyl 3,4-dimethylphenyl —C(O)CH₂C₆H₅4-methoxyphenyl 3,4-dimethylphenyl —C(O)CH₂OC₆H₅ 4-methoxyphenyl3,4-dimethylphenyl —C(O)isoxazol-5-yl 4-methoxyphenyl 3,4-dimethylphenyl—C(O)pyrazin-2-yl 4-methoxyphenyl 4-tert-butylphenyl —C(O)CH₃4-methoxyphenyl 4-tert-butylphenyl —C(O)OCH₃ 4-methoxyphenyl4-tert-butylphenyl —C(O)(cyclopropyl) 4-methoxyphenyl 4-tert-butylphenyl—C(O)OC(CH₃)₃ 4-methoxyphenyl 4-tert-butylphenyl —C(O)CH₂N(CH₃)benzyl4-methoxyphenyl 4-tert-butylphenyl —C(O)CH₂N(CH₃)Boc 4-methoxyphenyl4-tert-butylphenyl —C(O)furan-2-yl 4-methoxyphenyl 4-tert-butylphenyl—C(O)C₆H₅ 4-methoxyphenyl 4-tert-butylphenyl —C(O)CH₂C₆H₅4-methoxyphenyl 4-tert-butylphenyl —C(O)CH₂OC₆H₅ 4-methoxyphenyl4-tert-butylphenyl —C(O)isoxazol-5-yl 4-methoxyphenyl 4-tert-butylphenyl—C(O)pyrazin-2-yl 4-methoxyphenyl 4-cyclopropylphenyl —C(O)CH₃4-methoxyphenyl 4-cyclopropylphenyl —C(O)OCH₃ 4-methoxyphenyl4-cyclopropylphenyl —C(O)(cyclopropyl) 4-methoxyphenyl4-cyclopropylphenyl —C(O)OC(CH₃)₃ 4-methoxyphenyl 4-cyclopropylphenyl—C(O)CH₂N(CH₃)benzyl 4-methoxyphenyl 4-cyclopropylphenyl—C(O)CH₂N(CH₃)Boc 4-methoxyphenyl 4-cyclopropylphenyl —C(O)furan-2-yl4-methoxyphenyl 4-cyclopropylphenyl —C(O)C₆H₅ 4-methoxyphenyl4-cyclopropylphenyl —C(O)CH₂C₆H₅ 4-methoxyphenyl 4-cyclopropylphenyl—C(O)CH₂OC₆H₅ 4-methoxyphenyl 4-cyclopropylphenyl —C(O)isoxazol-5-yl4-methoxyphenyl 4-cyclopropylphenyl —C(O)pyrazin-2-yl 4-methoxyphenyl4-(CHF₂O)phenyl —C(O)CH₃ 4-methoxyphenyl 4-(CHF₂O)phenyl —C(O)OCH₃4-methoxyphenyl 4-(CHF₂O)phenyl —C(O)(cyclopropyl) 4-methoxyphenyl4-(CHF₂O)phenyl —C(O)OC(CH₃)₃ 4-methoxyphenyl 4-(CHF₂O)phenyl—C(O)CH₂N(CH₃)benzyl 4-methoxyphenyl 4-(CHF₂O)phenyl —C(O)CH₂N(CH₃)Boc4-methoxyphenyl 4-(CHF₂O)phenyl —C(O)furan-2-yl 4-methoxyphenyl4-(CHF₂O)phenyl —C(O)C₆H₅ 4-methoxyphenyl 4-(CHF₂O)phenyl —C(O)CH₂C₆H₅4-methoxyphenyl 4-(CHF₂O)phenyl —C(O)CH₂OC₆H₅ 4-methoxyphenyl4-(CHF₂O)phenyl —C(O)isoxazol-5-yl 4-methoxyphenyl 4-(CHF₂O)phenyl—C(O)pyrazin-2-yl 4-methoxyphenyl 4-(CH₃O)phenyl —C(O)CH₃4-methoxyphenyl 4-(CH₃O)phenyl —C(O)OCH₃ 4-methoxyphenyl 4-(CH₃O)phenyl—C(O)(cyclopropyl) 4-methoxyphenyl 4-(CH₃O)phenyl —C(O)OC(CH₃)₃4-methoxyphenyl 4-(CH₃O)phenyl —C(O)CH₂N(CH₃)benzyl 4-methoxyphenyl4-(CH₃O)phenyl —C(O)CH₂N(CH₃)Boc 4-methoxyphenyl 4-(CH₃O)phenyl—C(O)furan-2-yl 4-methoxyphenyl 4-(CH₃O)phenyl —C(O)C₆H₅ 4-methoxyphenyl4-(CH₃O)phenyl —C(O)CH₂C₆H₅ 4-methoxyphenyl 4-(CH₃O)phenyl —C(O)CH₂OC₆H₅4-methoxyphenyl 4-(CH₃O)phenyl —C(O)isoxazol-5-yl 4-methoxyphenyl4-(CH₃O)phenyl —C(O)pyrazin-2-yl

Compounds of the present invention include compounds having FormulaXVII, or a pharmaceutically acceptable salt form thereof:

wherein non-limiting examples of R, R¹, and R² are defined herein belowin Table IX. TABLE IX R R¹ R² 4-methoxyphenyl 3,4-dimethylphenyl—CH₂(cyclopropyl) 4-methoxyphenyl 3,4-dimethylphenyl —CH₂C₆H₅4-methoxyphenyl 3,4-dimethylphenyl —CH₂CH₂C₆H₅ 4-methoxyphenyl3,4-dimethylphenyl —CH₂C₆H₄(4-CN) 4-methoxyphenyl 3,4-dimethylphenyl—CH₂C₆H₄(4-F) 4-methoxyphenyl 3,4-dimethylphenyl —CH₂C₆H₄[4-N(CH₃)₂]4-methoxyphenyl 3,4-dimethylphenyl —CH₂C₆H₄[4-N(C₂H₅)₂] 4-methoxyphenyl3,4-dimethylphenyl —CH₂C₆H₄(4-imidazolyl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂(imidazol-1-yl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂(pyridine-2-yl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂(pyridine-3-yl) 4-methoxyphenyl3,4-dimethylphenyl —CH₂(pyridine-4-yl) 4-methoxyphenyl4-tert-butylphenyl —CH₂(cyclopropyl) 4-methoxyphenyl 4-tert-butylphenyl—CH₂C₆H₅ 4-methoxyphenyl 4-tert-butylphenyl —CH₂CH₂C₆H₅ 4-methoxyphenyl4-tert-butylphenyl —CH₂C₆H₄(4-CN) 4-methoxyphenyl 4-tert-butylphenyl—CH₂C₆H₄(4-F) 4-methoxyphenyl 4-tert-butylphenyl —CH₂C₆H₄[4-N(CH₃)₂]4-methoxyphenyl 4-tert-butylphenyl —CH₂C₆H₄[4-N(C₂H₅)₂] 4-methoxyphenyl4-tert-butylphenyl —CH₂C₆H₄(4-imidazolyl) 4-methoxyphenyl4-tert-butylphenyl —CH₂(imidazol-1-yl) 4-methoxyphenyl4-tert-butylphenyl —CH₂(pyridine-2-yl) 4-methoxyphenyl4-tert-butylphenyl —CH₂(pyridine-3-yl) 4-methoxyphenyl4-tert-butylphenyl —CH₂(pyridine-4-yl) 4-methoxyphenyl4-cyclopropylphenyl —CH₂(cyclopropyl) 4-methoxyphenyl4-cyclopropylphenyl —CH₂C₆H₅ 4-methoxyphenyl 4-cyclopropylphenyl—CH₂CH₂C₆H₅ 4-methoxyphenyl 4-cyclopropylphenyl —CH₂C₆H₄(4-CN)4-methoxyphenyl 4-cyclopropylphenyl —CH₂C₆H₄(4-F) 4-methoxyphenyl4-cyclopropylphenyl —CH₂C₆H₄[4-N(CH₃)₂] 4-methoxyphenyl4-cyclopropylphenyl —CH₂C₆H₄[4-N(C₂H₅)₂] 4-methoxyphenyl4-cyclopropylphenyl —CH₂C₆H₄(4-imidazolyl) 4-methoxyphenyl4-cyclopropylphenyl —CH₂(imidazol-1-yl) 4-methoxyphenyl4-cyclopropylphenyl —CH₂(pyridine-2-yl) 4-methoxyphenyl4-cyclopropylphenyl —CH₂(pyridine-3-yl) 4-methoxyphenyl4-cyclopropylphenyl —CH₂(pyridine-4-yl) 4-methoxyphenyl 4-(CHF₂O)phenyl—CH₂(cyclopropyl) 4-methoxyphenyl 4-(CHF₂O)phenyl —CH₂C₆H₅4-methoxyphenyl 4-(CHF₂O)phenyl —CH₂CH₂C₆H₅ 4-methoxyphenyl4-(CHF₂O)phenyl —CH₂C₆H₄(4-CN) 4-methoxyphenyl 4-(CHF₂O)phenyl—CH₂C₆H₄(4-F) 4-methoxyphenyl 4-(CHF₂O)phenyl —CH₂C₆H₄[4-N(CH₃)₂]4-methoxyphenyl 4-(CHF₂O)phenyl —CH₂C₆H₄[4-N(C₂H₅)₂] 4-methoxyphenyl4-(CHF₂O)phenyl —CH₂C₆H₄(4-imidazolyl) 4-methoxyphenyl 4-(CHF₂O)phenyl—CH₂(imidazol-1-yl) 4-methoxyphenyl 4-(CHF₂O)phenyl —CH₂(pyridine-2-yl)4-methoxyphenyl 4-(CHF₂O)phenyl —CH₂(pyridine-3-yl) 4-methoxyphenyl4-(CHF₂O)phenyl —CH₂(pyridine-4-yl) 4-methoxyphenyl 4-(CH₃O)phenyl—CH₂(cyclopropyl) 4-methoxyphenyl 4-(CH₃O)phenyl —CH₂C₆H₅4-methoxyphenyl 4-(CH₃O)phenyl —CH₂CH₂C₆H₅ 4-methoxyphenyl4-(CH₃O)phenyl —CH₂C₆H₄(4-CN) 4-methoxyphenyl 4-(CH₃O)phenyl—CH₂C₆H₄(4-F) 4-methoxyphenyl 4-(CH₃O)phenyl —CH₂C₆H₄[4-N(CH₃)₂]4-methoxyphenyl 4-(CH₃O)phenyl —CH₂C₆H₄[4-N(C₂H₅)₂] 4-methoxyphenyl4-(CH₃O)phenyl —CH₂C₆H₄(4-imidazolyl) 4-methoxyphenyl 4-(CH₃O)phenyl—CH₂(imidazol-1-yl) 4-methoxyphenyl 4-(CH₃O)phenyl —CH₂(pyridine-2-yl)4-methoxyphenyl 4-(CH₃O)phenyl —CH₂(pyridine-3-yl) 4-methoxyphenyl4-(CH₃O)phenyl —CH₂(pyridine-4-yl)

Compounds of the present invention include compounds having FormulaXVIII or XIX, or a pharmaceutically acceptable salt form thereof:

wherein R, R¹, n, and R⁴ are defined herein.

Exemplary compounds of Formula IX can be prepared by the proceduresoutlined in Example 1 below. The skilled practitioner will know how tosubstitute the appropriate reagents, starting materials and purificationmethods known to those skilled in the art, in order to prepareadditional compounds of the present invention.

EXAMPLE 1 Compound 1:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Step A: Preparation of 3,4-dimethyl-[(1E)-2-nitroethenyl]benzene: Asolution of 3,4-dimethylbenzaldehyde (20 mL, 0.15 mol), ammonium acetate(12.5 g, 0.16 mol), glacial acetic acid (65 mL), nitromethane (34 mL,0.63 mol), and acetic anhydride (3.0 mL, 0.032 mol) is refluxed for 2hours. The reaction is concentrated to an oil, then dichloromethane (100mL) is added, and the solution is washed with water (2×) and brine. Theorganic phase is dried (MgSO₄), and concentrated to a dark green solid.This material is re-crystallized (treated with Darco) from 50%cyclohexane/hexanes to afford 17.6 g (66% yield) of the desiredcompound. ¹H NMR (CDCl₃) δ 8.08 (dd, J=2.4 Hz, 13.5 Hz, 1H), 7.61 (dd,J=2.4 Hz, 13.5 Hz, 1H), 7.31-7.36 (m, 2H), 7.25 (d, J=7.8 Hz, 1H), 2.36(s, 3H), 2.35 (s, 3H); MS 329 (MH⁺).

Step B: Preparation ofN-[2-(4-methoxyphenyl)ethyl]-3,4-dimethyl-(α-nitromethyl)-benzenemethanaminehydrochloride: To a solution of3,4-dimethyl-[(1E)-2-nitroethenyl]benzene (10.1 g, 0.057 mol) in THF (28mL) at 21° C. is added 4-methoxyphenylethylamine (3.0 mL, 0.055 mol)dropwise over 6 minutes, keeping the temp below 30° C. with a waterbath. The reaction is stirred for 24 minutes at ambient temperature,cooled in an ice bath, diluted with ether (80 mL), and 2 N HCl/ether (34mL, 0.1068 mol) is added slowly, keeping the temperature below 15° C.The mixture is stirred in the cold for 30 minutes and the off-whitesolid which forms is collected by filtration to afford 18.4 g (89%yield) of the desired compound. ¹H NMR (CDCl₃) δ 10.7 (m, 1H), 10.3 (m,1H), 7.39-7.44 (m, 2H), 7.25 (d, J=7.2 Hz, 1H), 7.12 (m, 2H), 6.82 (m,2H), 5.77 (m, 1H), 5.23 (m, 1H), 4.87 (m, 1H), 3.79 (s, 3H), 3.29 (m,1H), 3.15 (m, 1H), 3.02 (m, 2H), 2.32 (s, 3H), 2.30 (s, 3H); MS 329(MH⁺).

Step C: Preparation ofN¹-[2-(4-methoxyphenyl)ethyl]-1-(3,4-dimethylphenyl)-1,2-ethanediamine:To a mixture ofN-[2-(4-methoxyphenyl)ethyl]-3,4-dimethyl-(α-nitromethyl)-benzenemethanaminein absolute ethanol (76 mL) at room temperature is added concentratedHCl (76 mL) slowly, keeping the temperature at less than 37° C. with awater bath. The mixture is cooled in an ice bath to 5° C. and zinc dust(11 g, 0.17 mol) is added in portions (starting with 0.5 g addition)over 50 minutes at less than 12° C. The reaction is stirred for 5minutes and the ice bath is removed. The reaction temperature risesquickly to about 20° C. and the reaction is maintained below about 32°C. with an ice bath. The reaction is stirred for 70 minutes at 20° C. to27° C. and any unreacted zinc is removed by filtration. The volume ofthe filtrate is reduced in vacuo then diluted with water (25 mL) anddichloromethane (150 mL). To the stirred mixture is added concentratedammonium hydroxide (140 mL), keeping the temperature below about 32° C.with an ice bath. The organic phase is separated, washed with brine,dried (Na₂SO₄), and concentrated to afford 12 g (quantitative yield) ofthe desired compound as an oil. MS 299 (MH⁺).

Step D: Preparation of1-[2-(4-methoxyphenyl)ethyl]-5-(3,4-dimethylphenyl)-2-imidazolidinone:To a solution ofN¹-[2-(4-methoxyphenyl)ethyl]-1-(3,4-dimethylphenyl)-1,2-ethanediamine(10.6 g, 0.0356 mol) in dry DMF (55 mL) is added1,1′-carbonyldiimidazole (6.4 g, 0.0395 mol). The reaction is stirred at50° C. for 30 minutes, cooled, diluted with ethyl acetate (300 mL), andwashed with 0.5 N HCl and brine. The organic phase is dried (MgSO₄), andconcentrated. The residue is re-crystallized from ethyl acetate (70 mL)to afford 7.5 g (65% yield) of the desired compound. ¹H NMR (CDCl₃) δ7.16 (d, J=7.8 Hz, 2H), 7.05 (m, 4H), 6.84 (d, J=7.8 Hz, 2H), 4.50 (t,J=8.1 Hz, 1H), 3.82 (s, 3H), 3.73-3.65 (m, 2H), 3.27 (t, J=8.4 Hz, 1H),2.91 (m, 1H), 2.78 (m, 1H), 2.68 (m, 1H), 2.30 (s, 6H). MS 325 (MH⁺).Anal. Calcd. For C₂₀H₂₄N₂O₂¼H₂O: C, 73.03; H, 7.51; N, 8.52. Found: C,73.29; H, 7.19; N, 8.32.

Step E: Preparation of1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinonehydrochloride: To a solution of1-[2-(4-methoxyphenyl)ethyl]-5-(3,4-dimethylphenyl)-2-imidazolidinone(2.0 g, 0.0062 mol) in glacial acetic acid (21 mL) is added a solutionof sodium nitrite (0.58 g, 0.0084 mol) in H₂O (2.8 mL) at roomtemperature over 2 minutes. The solution is stirred for 30 minutes andthen cooled to 8° C. Zinc dust (0.84 g, 0.013 mol) is added at 8° C. to18° C. in portions and the mixture is stirred two hours at 12° C. to 18°C. The reaction is cooled in an ice bath and dichloromethane (20 mL) andH₂O (20 mL) are added. Then concentrated ammonium hydroxide (34 mL) isadded slowly, maintaining the temperature below 25° C. The organic layeris separated, washed with brine, dried (Na₂SO₄), treated with 2 MHCl/ether (3.3 mL) and concentrated. The residue is heated in ethylacetate (8 mL) and diluted slowly with hexanes (30 mL). The resultingsolid is collected and triturated with 20% ether/hexanes (50 mL). Thesolid is collected and re-crystallized from ethyl acetate (8 mL) toafford 1.88 g (81% yield) of the desired compound. ¹H NMR (CDCl₃) δ 7.06(m, 3H), 6.95 (d, J=8.1 Hz, 2H), 6.74 (d, J=8.1 Hz, 2H), 4.42 (m, 1H),4.25 (m, 1H), 3.90 (m, 1H), 3.75 (s, 3H), 3.60 (m, 1H), 2.89 (m, 1H),2.71 (m, 1H), 2.58 (m, 1H), 2.21 (s, 3H), 2.20 (s, 3H). MS 340 (MH⁺).Anal. calcd. for C₂₀H₂₅N₃O₂HCl: C, 63.91, H, 6.97; N, 11.18. Found: C,63.71, H, 6.67; N, 11.18.

Exemplary compounds of the present invention can be prepared utilizingthe following procedure described in Example 2 for preparingintermediates such asN¹-[2-(4-methoxyphenyl)ethyl]-1-(4-methoxyphenyl)-1,2-ethanediaminewhich can be suitably used to prepare the compounds according to thepresent invention. This procedure can be coupled with steps (D) and (E)from Example 1 to prepare exemplary 1-N-amino-2-imidazolidinonecompounds of the present invention.

EXAMPLE 2N¹-[2-(4-methoxyphenyl)ethyl]-1-(4-methoxyphenyl)-1,2-ethanediamine

Preparation of (4-methoxyphenyl)-trimethylsilanyloxyacetonitrile: To asolution of 4-methoxybenzaldehyde (1 mL, 8.2 mmol) and trimethylsilylcyanide (1.3 mL, 10.25 mmol) is added zinc iodide (50 mg, 0.15 mmol).The resulting exothermic reaction is controlled using an ice-bath. Thetemperature is maintained below 65° C. The reaction is allowed to cooland the crude material is used without isolation.

Preparation of(4-methoxyphenyl)-[2-(4-methoxyphenyl)ethylamino]acetonitrile:4-Methoxyphenethylamine (1.2 mL, 8.2 mmol) and methanol (0.5 mL) areadded to the crude material obtained above. The solution is heated to125° C. for 15 minutes in a microwave reaction vessel after which thesolution is concentrated in vacuo and the crude product obtained is usedwithout further purification.

Preparation ofN¹-[2-(4-methoxyphenyl)ethyl]-1-(4-methoxyphenyl)-1,2-ethanediamine: Thecrude (4-methoxyphenyl)-[2-(4-methoxyphenyl)ethylamino]-acetonitrileobtained in the above procedure is dissolved in diethyl ether (20 mL)and this solution is slowly added to an ice-cold solution of lithiumaluminum hydride (1.0M, 16 mL, 16 mmol) in diethyl ether. The coolingbath is removed and the solution is allowed to stir for 1 hour. Thereaction solution is then re-cooled to 5° C. and water (4 mL) is added,followed by 3N NaOH (3 mL). The ether is then decanted from theresulting solid and the solid is again washed with diethyl ether (20mL). The combined ether washings are dried (Na₂SO₄) and concentrated invacuo to afford 2.5 g (quantitative yield) of the desired compound. MS(301) (MH⁺).

The following are non-limiting examples of compounds of Formula IX.

Compound 2:1-Amino-4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone.An alternative name for this compound is1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone.¹H-NMR (DMSO-d₆): δ 7.47 (d, J=8.1 Hz, 2H), 7.33 (d, J=8.1 Hz, 2H), 7.04(d, J=8.4 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.67 (t, J=7.8 Hz, 1H), 3.87(t, J=7.8 Hz, 1H), 3.71 (s, 3H), 3.55 (m, 1H), 3.34 (t, J=8.1 Hz, 1H),2.64 (m, 5H), 1.29 (s, 9H). MS m/z (ESI, positive): 368 [M+H]⁺.

Compound 3:1-Amino-4-(4-methoxyphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-imidazolidinone.An alternative name for this compound is1-Amino-3-[3-(4-methoxyphenyl)propyl]-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 7.49 (d, J=8.1 Hz, 2H), 7.32 (d, J=9.0 Hz, 2H), 7.11(d, J=8.1 Hz, 2H), 7.03 (d, J=8.7 Hz, 2H), 6.99 (d, J=8.4 Hz, 2H), 6.80(d, J=9.0 Hz, 2H), 4.78 (t, J=7.8 Hz, 1H), 3.86 (t, J=7.8 Hz, 1H), 3.77(s, 3H), 3.70 (s, 3H), 3.29 (m, 2H), 2.51 (m, 1H), 2.39 (m, 2H), 2.28(s, 3H), 1.56 (m, 2H). MS 356 (MH⁺). Anal. Calcd. For C₂₇H₃₃N₃O₆S: C,61.46; H, 6.30; N, 7.96. Found: C, 61.92; H, 6.29; N, 7.86.

Compound 4:1-Amino-4-(4-cyclopropylphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-imidazolidinone.An alternative name for this compound is1-Amino-3-[3-(4-methoxyphenyl)propyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 7.55 (d, J=8.1 Hz, 2H), 7.28 (d, J=8.1 Hz, 2H), 7.13(m, 4H), 7.03 (d, J=8.7 Hz, 2H), 6.81 (d, J=8.7 Hz, 2H), 4.80 (t, J=7.8Hz, 1H), 3.90 (t, J=7.8 Hz, 1H), 3.71 (s, 3H), 3.32 (m, 2H), 2.67 (m,1H), 2.40 (m, 2H), 2.29 (s, 3H), 1.93 (m, 1H), 1.57 (m, 2H), 0.96 (m,2H), 0.69 (m, 2H). MS 366 (MH⁺). Anal. Calcd. For C₂₉H₃₅N₃O₅S: C, 64.78;H, 6.56; N, 7.82. Found: C, 63.90; H, 6.43; N, 7.52.

Compound 5:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-difluoromethoxyphenyl)-2-imidazolidinone4-methylbenzenesulfonic acid salt. ¹H NMR (CDCl₃) δ 7.79 (d, J=8.1 Hz,2H), 7.06 (m, 4H), 6.91 (m, 4H), 6.75 (d, J=8.7 Hz, 2H), 6.49 (t, J=73.5Hz, 1H), 4.27 (t, J=8.1, 1H), 3.98 (t, J=8.1 Hz, 1H), 3.76 (s, 3H), 3.52(m, 2H), 2.73 (m, 1H), 2.64 (m, 1H), 2.50 (m, 1H), 2.28 (s, 3H). MS 378(MH⁺). Anal. calcd. for C₁₉H₂₁F₂N₃O₃.C₇H₈O₃S: C, 56.82, H, 5.32; N,7.65. Found: C, 57.04, H, 5.22; N, 7.52.

Compound 6:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone4-methylbenzenesulfonic acid salt. ¹H NMR (CDCl₃) δ 7.50 (m, 2H), 7.27(d, J=8.4 Hz, 2H), 7.14 (m, 4H), 7.05 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.7Hz, 2H), 4.68 (t, J=8.1 Hz, 1H), 3.84 (t, J=7.8 Hz, 1H), 3.73 (s, 3H),3.56 (m, 1H), 3.23 (t, J=8.1 Hz, 1H), 2.77 (m, 1H), 2.65 (m, 1H), 2.62(m, 1H), 2.21 (s, 3H), 2.30 (s, 3H), 1.95 (m, 1H), 0.98 (m, 2H), 0.71(m, 2H). MS 352 (MH⁺). Anal. calcd. for C₂₁H₂₅N₃O₂ C₇H₈O₃S.¼H₂O: C,63.68; H, 6.39; N, 7.96. Found: C, 63.65; H, 6.35; N, 7.94.

Exemplary compounds having Formula XI can be prepared by the proceduredescribed in Example 3 herein below. The skilled practitioner will knowhow to substitute the appropriate reagents, starting materials andpurification methods known to those skilled in the art, in order toprepare additional compounds of the present invention.

EXAMPLE 3 Compound 7:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Preparation of1-(methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:A solution of1-amino-3-[2-(4-methoxyphenyl)-ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinonehydrochloride (300 mg, 0.80 mmol) in dichloromethane (3.0 mL) andHunig's base (0.31 mL, 1.8 mmol) is cooled in an ice bath andmethanesulfonyl chloride (0.068 mL, 0.88 mmol) is added dropwise. Thereaction is stirred cold for 45 minutes and washed with 0.1 N HCl (2×)and H₂O. The organic phase is dried (Na₂SO₄), and concentrated to awhite foam. The crude material is purified over silica (1.5%MeOH/dichloromethane) to afford 161 mg (48% yield) of the desiredcompound. ¹H NMR (CDCl₃) δ 7.17 (d, J=8.1 Hz, 1H), 7.07 (m, 2H), 7.00(m, 2H), 6.85 (m, 3H), 4.45 (t, J=8.1 Hz, 1H), 3.96 (t, J=8.1 Hz, 1H),3.81 (s, 3H), 3.74 (m, 1H), 3.33 (t, J=8.4 Hz, 1H), 3.06 (s, 3H), 2.97(m, 1H), 2.76 (m, 1H), 2.67 (m, 1H), 2.30 (s, 6H).). MS 418 (MH⁺). Anal.Calcd. for C₂₁H₂₇N₃O₄S¼H₂O: C, 59.77, H, 6.57; N, 9.96. Found: C, 59.82,H, 6.06; N, 9.85. FAB-HRMS: anal. calcd for C₂₁H₂₇N₃O₄S: 418.18005.Found: 418.17960.

The following are non-limiting examples of compounds of Formula XI.

Compound 8:1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H-NMR (CDCl₃) δ: 7.59 (s, 1H), 7.17 (d, J=8.4 Hz, 2H), 7.06 (m, 4H),6.84 (d, J=9 Hz, 2H), 5.37 (s, 2H), 4.49 (t, J=8.1 Hz, 1H), 4.00 (t,J=8.1 Hz, 1H), 3.81 (s, 3H), 3.42 (t, J=8.1 Hz, 1H), 2.95 (m, 1H), 2.7(m, 2H), 2.29 (d, J=2.7 Hz, 6H). MS m/z (ESI, positive): 418 [M+H]⁺, 440[M+Na]⁺. Anal Calcd for C₂₀H₂₆N₄O₄S: C, 57.40; H, 6.26; N, 13.39. Found:C, 57.64; H, 6.40; N, 13.10.

Compound 9:1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H-NMR (CDCl₃) δ: 7.93 (s, 1H), 7.39 (d, J=7.2 Hz, 2H), 7.22 (d, J=7.5Hz, 2H), 7.05 (d, J=7.5 Hz, 2H), 6.81 (d, J=7.2 Hz, 2H), 5.67 (s, 2H),4.52 (t, J=8.4 Hz, 1H), 4.01 (t, J=8.4 Hz, 1H), 3.78 (s, 3H), 3.65 (m,1H), 3.44 (t, J=8.4 Hz, 1H), 2.96 (m, 1H), 2.71 (m, 2H), 1.33 (s, 9H).MS m/z (ESI, positive): 447 [M+H]⁺. Anal calcd for C₂₂H₃₀N₄O₄S: C,59.17; H, 6.77; N, 12.55. Found: C, 59.52; H, 6.98; N, 12.46.

Compound 10:1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-cyclopropyl)-phenyl]-2-imidazolidinone:¹H NMR δ (DMSO-d₆) 8.6 (s, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.15 (d, J=7.8Hz, 2H), 7.0 (m, 4H), 6.85 (d, J=7.8 Hz, 2H), 4.55 (t, J=7 Hz, 1H), 3.9(t, J=6 Hz, 1H), 3.75 (s, 3H), 3.4 (m, 2H), 2.7 (m, 2H), 2.45 (m, 1H),1.9 (m, 1H), 1.0 (m, 2H), 0.75 (m, 2H). Anal. calcd. for C₂₁H₂₆N₄O₄S0.25H₂O: C, 57.99; H, 6.13; N, 12.88; found C, 53.11; H, 6.17; N, 12.52.FAB-HRMS calcd. 431.1753; found 431.1757 (MH⁺).

Compound 11:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-tert-butyl)benzyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.4 (s, 1H) 7.35 (d, J=7.8 Hz, 2H), 7.2 (d, J=7.8 Hz,2H), 7.1 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 3.8 (m, 1H), 3.7 (s,3H), 3.5 (m, 1H), 3.3 (m, 1H), 3.25-3.1 (m, 2H), 3.0 (m, 1H), 2.85 (s,3H), 2.8-2.5 (m, 3H), 1.25 (s, 9H). Anal. calcd. for C₂₄H₃₃N₃O₄S: C,62.72; H, 7.24; N, 9.14; found C, 62.49; H, 7.01; N, 8.91. FAB-HRMScalcd. 460.2270; found 460.2284 (MH⁺).

Compound 12:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(3-methyl-4-methoxy)phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.5 (s, 1H), 7.16 (d, J=7.8 Hz, 1H), 7.12 (s, 1H)7.05 (d, J=7.8 Hz, 2H), 6.95 (d, J=7.8 Hz, 1H), 6.8 (d, J=7.8 Hz, 2H),4.55 (t, J=8 Hz, 1H), 3.85 (m, 1H), 3.8 (s, 3H), 3.7 (s, 3H), 3.5 (m,1H), 3.25 (m, 1H), 3.0 (s, 3H), 2.85-2.55 (m, 3H), 2.2 (s, 3H). FAB-HRMScalcd. for C₂₁H₂₇N₃O₅S: 434.1750; found 434.1751 (MH⁺).

Compound 13:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(3-methoxy-4-methyl)phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.5 (s, 1H), 7.2 (d, J=7.8 Hz, 1H), 7.1 (d, J=8.4 Hz,2H), 6.95 (s, 1H), 6.85 (m, 3H), 4.6 (t, J=8 Hz, 1H), 3.85 (m, 1H), 3.8(s, 3H), 3.7 (s, 3H), 3.5 (m, 1H), 3.3 (m, 1H), 3.0 (s, 3H), 2.85-2.55(m, 3H), 2.2 (s, 3H). Anal. calcd. for C₂₁H₂₈N₃O₅S: C, 58.18; H, 6.28;N, 9.69; found C, 57.94; H, 6.45; N, 9.32. FAB-HRMS calcd. 434.1750;found 434.1752 (MH⁺).

Compound 14:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-isopropyloxy)-phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.5 (s, 1H), 7.3 (d, J=7.8 Hz, 2H), 7.1 (d, J=8.4 Hz,2H), 7.0 (d, J=8.4 Hz, 2H), 6.9 (d, J=7.8 Hz, 2H), 4.6 (m, 1H), 3.85 (m,1H), 3.75 (s, 3H), 3.4 (m, 1H), 3.25 (m, 1H), 3.0 (s, 3H), 2.8-2.5 (m,3H), 1.3 (d, 6H). Anal. calcd. for C₂₂H₂₉N₃O₅S 0.25H₂O: C, 58.46; H,6.57; N, 9.29; found C, 58.42; H, 6.56; N, 9.15. FAB-HRMS calcd.448.1906; found 448.1912 (MH⁺).

Compound 15:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(benzo[1,3]dioxol-5-yl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.45 (s, 1H), 7.05 (d, J=7.8 Hz, 2H), 6.9-6.8 (m,5H), 6.0 (s, 2H), 4.6 (t, J=6 Hz, 1H), 3.8 (t, J=6 Hz, 1H), 3.7 (s, 3H),3.5 (m, 1H), 3.3 (t, J=7 Hz, 1H), 3.0 (s, 3H), 2.85-2.55 (m, 3H). Anal.calcd. for C₂₀H₂₃N₃O₆S 0.5H₂O: C, 54.29; H, 5.46; N, 9.49; found C,54.67; H, 5.31; N, 9.41. FAB-HRMS calcd. 434.1386; found 434.1365 (MH⁺).

Compound 16:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(2,2-difluorobenzo-[1,3]dioxol-5-yl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.5 (s, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.35 (s, 1H),7.25 (d, J=7.8 Hz, 1H), 7.1 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H),4.7 (t, J=6 Hz, 1H), 3.9 (t, J=7 Hz, 1H), 3.8 (s, 3H), 3.5 (m, 1H), 3.25(t, J=7 Hz, 1H), 3.0 (s, 3H), 2.9-2.55 (m, 3H). Anal. calcd. forC₂₀H₂₁F₂N₃O₆S: C, 51.17; H, 4.51; N, 8.95; found C, 51.20; H, 4.66; N,8.63. FAB-HRMS calcd. 470.1197; found 470.1190 (MH⁺).

Compound 17:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3-dihydro-benzo[1,4]dioxin-6-yl)]-2-imidazolidinone:¹H NMR δ (DMSO-d₆) δ 9.5 (s, 1H), 7.1 (d, J=7.8 Hz, 2H), 6.9-6.8 (m,5H), 4.55 (t, J=8 Hz, 1H), 4.25 (s, 4H), 3.8 (t, J=8 Hz, 1H), 3.7 (s,3H), 3.5 (m, 1H), 3.25 (t, J=8 Hz, 1H), 2.8-2.55 (m, 3H). Anal. calcd.for C₂₁H₂₅N₃O₆S 0.5H₂O: C, 55.25; H, 5.73; N, 9.20; found C, 55.58; H,5.67; N, 9.22. FAB-HRMS calcd. 448.1542; found 448.1538 (MH⁺).

Compound 18:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(2,2-dimethylbenzo-[1,3]dioxol-5-yl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.45 (s, 1H), 7.1 (d, J=7.8 Hz, 2H), 6.9-6.8 (m, 5H),4.6 (t, J=6 Hz, 1H), 3.8 (t, J=6 Hz, 1H), 3.7 (s, 3H), 3.5 (m, 1H), 3.3(t, J=7 Hz, 1H), 3.0 (s, 3H), 2.85-2.55 (m, 3H), 1.8 (s, 6H). Anal.calcd. for C₂₂H₂₇N₃O₆S.0.2H₂O: C, 56.81; H, 5.93; N, 9.03; found C,57.14; H, 5.94; N, 8.68; FAB-HRMS calcd. 462.1699; found 462.1718 (MH⁺).

Compound 19:1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)methyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.34 (s, 1H), 7.12 (q, J=8.4 Hz, 6.3 Hz, 4H), 7.01 (d,J=8.1 Hz, 2H), 6.84 (d, J=7.8 Hz, 2H), 4.80 (d, J=14.7 Hz, 1H), 4.34 (t,J=8.4 Hz, 1H), 3.94 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.58 (d, J=14.7 Hz,1H), 3.40 (t, J=8.4 Hz, 1H), 3.18 (s, 3H), 1.93 (m, 1H), 1.02 (m, 2H),0.73 (m, 2H). (MS) 416 (MH⁺), 438 (MNa⁺). HRMS found for C₂₁H₂₆N₃O₄S.

Compound 20:1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.31 (s, 1H), 7.22 (d, J=8.1 Hz, 2H), 7.17 (d, J=8.4Hz, 2H), 7.06 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.7 Hz, 2H), 4.47 (t, J=8.4Hz, 1H), 3.97 (t, J=8.4 Hz, 2H), 3.79 (s, 3H), 3.72 (m, 1H), 3.36 (t,J=8.4 Hz, 1H), 3.08 (s, 3H), 2.96 (m, 1H), 2.76 (m, 1H), 2.66 (m, 1H),2.39 (s, 3H). MS 404 (MH⁺). Anal. Calcd for C₂₀H₂₅N₃O₄S: C, 59.53; H,6.25; N, 10.41. Found: C, 59.91; H, 6.44; N, 10.55.

Compound 21:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-chlorophenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.37 (d, J=8.4 Hz, 2H), 7.19 (m, 3H), 7.04 (d, J=8.4Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 4.44 (t, J=7.8 Hz, 1H), 3.95 (t, J=8.4Hz, 1H), 3.79 (s, 3H), 3.72 (m, 1H), 3.32 (t, J=8.1 Hz, 1H), 3.07 (s,3H), 2.93 (m, 1H), 2.69 (m, 2H). MS (424) (MH⁺), 446 (MNa⁺), 422 (M−H⁻).Anal. Calcd for C₁₉H₂₂ClN₃O₄S: C, 53.83; H, 5.23; N, 9.91. Found: C,55.51; H, 5.56; N, 9.38.

Compound 22:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-trifluoromethyl-phenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.67 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.1 Hz, 2H), 7.13(s, 1H), 7.05 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 4.50 (t, J=8.1Hz, 1H), 3.98 (t, J=8.4 Hz, 1H), 3.77 (m, 4H), 3.56 (t, J=8.1 Hz, 1H),3.08 (s, 3H), 2.94 (m, 1H), 2.72 (m, 2H). (MS) 458 (MH⁺), 480 (MNa⁺).HRMS found for C₂₀H₂₃N₃O₄SF₃.

Compound 23:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.20 (d, J=8.7 Hz, 3H), 7.05 (d, J=8.7 Hz, 2H), 6.93(d, J=8.7 Hz, 2H), 6.84 (d, J=8.7 Hz, 2H), 4.45 (t, J=8.4 Hz, 1H), 3.96(t, J=8.25, 1H), 3.84 (s, 3H), 3.80 (s, 3H), 3.69 (m, 1H), 3.35 (t,J=8.55 Hz, 1H), 3.08 (s, 3H), 2.96 (m, 1H), 2.76 (m, 1H), 2.65 (m, 1H).MS (m/z ESI): 420 (MH⁺), 418 [M−H]⁻. Anal Calcd for C₂₀H₂₅N₃O₅S: C,57.26; H, 6.01; N, 10.02. Found: C, 57.18; H, 6.06; N, 9.98.

Compound 24:1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-imidazolidinone.An alternative name for compound 24 is1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.70 (d, J=8.4 Hz, 2H), 7.44 (d, J=8.4 Hz, 2H), 7.21(d, J=8.4 Hz, 2H), 7.11 (s, 1H), 6.85 (d, J=9 Hz, 2H), 4.49 (t, J=8.4Hz, 1H), 3.97 (t, J=8.4 Hz, 1H), 3.89 (t, J=8.4 Hz, 1H), 3.81 (s, 3H),3.76 (m, 1H), 3.08 (s, 3H), 2.99 (m, 1H), 2.71 (m, 2H), 1.36 (s, 9H). MSm/z (ESI, positive): 446 (MH⁺). Anal Calcd for C₂₃H₃₁N₃O₄S: C, 62.00; H,7.01; N, 9.43. Found: C, 61.93, 61.77; H, 6.62, 6.83; N, 9.11, 9.13.

Compound 25:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-diethylamino)-phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.45 (s, 1H), 7.1 (d, J=7.8 Hz, 2H), 7.0 (d, J=7.8Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 6.65 (d, J=7.8 Hz, 2H), 4.5 (t, J=8 Hz,1H), 3.75 (t, J=8 Hz, 1H), 3.7 (s, 3H), 3.45 (m, 2H), 3.35 (q, J=8 Hz,4H), 3.2 (t, J=8 Hz, 1H), 3.0 (s, 3H), 2.8-2.6 (m, 2H), 1.1 (t, J=8 Hz,6H). Anal. calcd. for C₂₃H₃₂N₄O₄S 0.5H₂O: C, 58.83; H, 7.07; N, 11.93;found C, 58.85; H, 7.04; N, 11.80. FAB-HRMS calcd. 461.2223; found461.2243 (MH⁺).

Compound 26:1-[(Methylsulfonyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-difluoro-methoxyphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.26 (d, J=8.7 Hz, 2H), 7.17 (d, J=8.4 Hz, 3H), 7.05(d, J=8.7 Hz, 2H), 6.93 (s, 1H), 6.84 (d, J=8.4 Hz, 2H), 6.56 (t, J=73.5Hz, 1H), 4.76 (t, J=8.1, 1H), 3.96 (t, J=8.7 Hz, 1H), 3.81 (s, 3H), 3.72(m, 1H), 3.34 (t, J=8.1 Hz, 1H), 3.07 (s, 3H), 2.96 (m, 1H), 2.75 (m,1H), 2.71 (m, 1H). MS 456 (MH⁺). Anal. calcd. for C₂₀H₂₃F₂N₃O₅S % H₂O:C, 52.22, H, 5.15; N, 9.14. Found: C, 52.12, H, 4.87; N, 8.92.

Compound 27:1-[(Methylsulfonyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-trifluoro-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.28 (s, 4H), 7.03 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4Hz, 2H), 6.72 (s, 1H), 4.47 (t, J=8.4, 1H), 3.97 (t, J=8.4 Hz, 1H), 3.82(s, 3H), 3.76 (m, 1H), 3.35 (t, J=8.4 Hz, 1H), 3.07 (s, 3H), 2.97 (m,1H), 2.76 (m, 1H), 2.70 (m, 1H). MS 496 (MH⁺). Anal. calcd. forC₂₀H₂₂F₃N₃O₅S: C, 50.74, H, 4.68; N, 8.87. Found: C, 50.74, H, 4.80; N,8.46.

Compound 28:1-[(Methylsulfonyl)amino]-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.11 (m, 7H), 6.83 (d, J=8.7 Hz, 2H), 4.45 (t, J=8.4Hz, 1H), 3.95 (t, J=8.4 Hz, 1H), 3.80 (s, 3H), 3.72 (m, 1H), 3.34 (t,J=8.4 Hz, 1H), 3.07 (s, 3H), 2.97 (m, 1H), 2.68 (m, 2H), 1.93 (m, 1H),1.02 (m, 2H), 0.74 (m, 2H). MS m/z (ESI, positive): 430 (MH⁺). Analcalcd for C₂₂H₂₇N₃O₄S: C, 61.52: H, 6.34; N, 9.78. Found: C, 61.74; H,6.20; N, 9.91.

Compound 29:1-(Cyclopropylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.37 (s, 1H), 7.17 (d, J=8.1 Hz, 2H), 7.04 (d, J=8.1Hz, 2H), 6.91 (d, J=7.8 Hz, 2H), 6.81 (d, J=7.8 Hz, 2H) 4.40 (t, J=8.1Hz, 1H), 3.91 (t, J=8.1 Hz, 1H), 3.81 (s, 3H), 3.75 (m, 5H), 3.34 (t,J=8.1 Hz, 1H), 2.93 (m, 1H), 2.71 (m, 1H), 2.63 (m, 2H), 1.23 (m, 2H),1.05 (m, 2H). MS 446 (MH⁺).

Compound 30:1-(Propylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.11 (m, 6H), 6.84 (m, 3H), 4.45 (t, J=8.4 Hz, 1H),3.96 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.72 (m, 1H), 3.34 (t, J=8.4 Hz,1H), 3.16 (t, J=7.8 Hz, 2H), 2.96 (m, 1H), 2.71 (m, 2H), 1.99 (m, 3H),1.12 (t, J=7.5 Hz, 3H), 1.02 (m, 2H), 0.75 (m, 2H). MS m/z (ESI,positive): 458 (MH⁺), (ESI negative): 456 [M−H]⁻. Anal calcd forC₂₄H₃₁N₃O₄S: C, 63.00; H, 6.83; N, 9.18. Found: C, 62.84; H, 7.05; N,9.31.

Compound 31:1-(Butylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.07 (m, 6H), 6.84 (m, 3H), 4.43 (t, J=8.4 Hz, 1H),3.94 (t, J=8.4 Hz, 1H), 3.80 (s, 3H), 3.70 (m, 1H), 3.33 (t, J=8.4 Hz,1H), 3.18 (t, J=7.8 Hz, 2H), 2.94 (m, 1H), 2.68 (m, 2H), 1.92 (m, 3H),1.50 (m, 2H), 1.00 (m, 5H), 0.72 (m, 2H). MS m/z (ESI, positive): 472(MH⁺), 494 [M+Na]⁺. Anal calcd for C₂₅H₃₃N₃O₄S: C, 63.67; H, 7.05; N,8.91. Found: C, 63.92; H, 6.80; N, 9.04.

Compound 32:1-(Butylsulfonylamino)-3-[(4-methoxyphenyl)-ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.43 (d, J=8.1 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.05(m, 3H), 6.84 (d, J=8.7 Hz, 2H), 4.47 (t, J=8.1 Hz, 1H), 3.97 (t, J=8.1Hz, 2H), 3.81 (s, 3H), 3.72 (m, 1H), 3.39 (t, J=8.4 Hz, 1H), 3.21 (t,J=7.8 Hz, 2H), 2.98 (m, 1H), 2.75 (m, 2H), 1.95 (m, 2H), 1.52 (m, 2H),1.36 (s, 9H), 1.02 (t, J=7.5 Hz, 3H). MS m/z (ESI, positive): 488 (MH⁺),510 [M+Na]⁺, (ESI negative): 486 [M−H]⁻. Anal calcd for C₂₆H₃₇N₃O₄S: C,64.04; H, 7.65; N, 8.62. Found: C, 63.94; H, 7.48; N, 8.90.

Compound 33:1-(Vinylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3-dihydrobenzo-[1,4]dioxin-6-yl)]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.7 (s, 1H), 7.1 (d, J=7.8 Hz, 2H), 6.9-6.9 (m, 6H),6.2 (d, J=9 Hz, 1H), 6.1 (d, J=8 Hz, 1H), 4.5 (m, 1H), 4.25 (s, 4H), 3.8(m, 1H), 3.75 (s, 3H), 3.4 (m, 2H), 3.2 (m, 1H), 2.75 (m, 2H). FAB-HRMScalcd. for C₂₂H₂₅N₃O₆S: 460.1542; found 460.1554 (MH⁺).

Compound 34:1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropyl-phenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 10.2 (s, 1H), 7.2 (d, J=7.8 Hz, 2H), 7.15 (d, J=7.8Hz, 2H), 7.0 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 5.5 (m, 1H), 5.3(m, 1H), 4.6 (t, J=8 Hz, 1H), 3.8 (t, J=8 Hz, 1H), 3.65 (s, 3H), 3.4 (m,1H), 3.2 (m, 1H), 2.8-2.6 (m, 2H) 1.9 (m, 1H), 0.9 (d, J=8 Hz, 2H), 0.7(d, J=4 Hz, 2H). Anal. calcd. for C₂₂H₂₆FN₃O₄S: C, 59.04; H, 5.86; N,9.39; found C, 59.02; H, 5.62; N, 9.11. FAB-HRMS calcd. 448.1706; found448.1710 (MH⁺).

Compound 35:1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxy-phenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 10.2 (s, 1H), 7.3 (d, J=7.8 Hz, 2H), 7.05 (d, J=7.8Hz, 2H), 7.0 (d, J=7.8 Hz, 2H), 6.85 (s, J=7.8 Hz, 2H), 5.5 (m, 1H),5.35 (m, 1H), 4.6 (t, J=8 Hz, 1H), 3.8 (t, J=8 Hz, 1H), 3.75 (s, 3H),3.7 (s, 3H), 3.4 (m, 1H), 3.35 (s, 1H), 3.2 (t, J=8 Hz, 1H), 2.8-2.6 (m,2H). Anal. calcd. for C₂₀H₂₄FN₃O₅S: C, 54.91; H, 5.53; N, 9.60; found C,54.63; H, 5.43; N, 9.67. FAB-HRMS calcd. 438.1449; found 438.1509 (MH⁺).

Compound 36:1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-tert-butyl-phenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 10.2 (s, 1H) 7.5 (d, J=7.8 Hz, 2H), 7.3 (d, J=7.8 Hz,2H), 7.05 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 5.5 (m, 1H), 5.3 (m,1H), 4.6 (t, J=8 Hz, 1H), 3.85 (t, J=8 Hz, 1H), 3.75 (s, 3H), 3.5 (m,1H), 3.3 (t, J=8 Hz, 1H), 2.8-2.6 (m, 2H) 1.3 (s, 9H). Anal. calcd. forC₂₃H₃₀FN₃O₄S: C, 59.59; H, 6.52; N, 9.06; found C, 59.61; H, 6.55; N,8.89. FAB-HRMS calcd. 464.2019; found 464.2023 (MH⁺).

Compound 37:1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3dihydro-benzo[b][1,4]dioxin-6-yl)]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 10.2 (s, 1H), 7.05 (d, J=7.8 Hz, 2H), 6.9 (d, J=7.8Hz 1H), 6.85 (m, 4H), 5.55 (m, 1H), 5.35 (m, 1H), 4.55 (t, J=7 Hz, 1H),4.25 (s, 4H), 3.8 (t, J=7 Hz, 1H), 3.7 (s, 3H), 3.5 (m, 2H), 3.2 (t, J=7Hz, 1H), 2.8-2.55 (m, 2H). Anal. calcd. for C₂₁H₂₄FN₃O₆S: C, 54.18; H,5.20; N, 9.03; found C, 54.53; H, 5.24; N, 8.78. FAB-HRMS calcd.466.1448; found 466.1458 (MH⁺).

Compound 38:1-(2,2,2-Trifluoroethanesulfonylamino)-4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone.¹H NMR (CDCl₃) δ 8.04 (s, 1H), 7.44 (d, J=8.1 Hz, 2H), 7.22 (d, J=8.1Hz, 2H), 7.08 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.1 Hz, 2H), 4.54 (t, J=8.7Hz, 1H), 4.04 (m, 3H), 3.79 (s, 3H), 3.74 (m, 1H), 3.40 (t, J=8.4 Hz,1H), 2.99 (m, 1H), 2.70 (m, 2H), 1.36 (s, 9H). MS m/z (ESI, positive):514 (MH⁺), 536 [M+Na]⁺, (ESI negative): 512 [M−H]⁻.

Compound 39:1-(Chloromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-tert-butyl-phenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.45 (d, J=7.8 Hz, 2H), 7.2 (d, J=7.8 Hz, 2H), 7.1 (s,1H), 7.05 (d, J=7.8 Hz, 2H), 6.85 (d, J=7.8 Hz, 2H), 4.65 (m, 2H), 4.45(t, J=8 Hz, 1H), 3.95 (t, J=8 Hz, 1H), 3.8 (s, 3H), 3.7 (m, 1H), 3.4 (t,J=8 Hz, 1H), 3.0 (m, 1H), 2.8-2.6 (m, 2H) 1.5 (s, 9H). Anal. calcd. forC₂₃H₃₀ClN₃O₄S: C, 57.55; H, 6.30; N, 8.75; found C, 57.71; H, 6.13; N,8.50. FAB-HRMS calcd. 480.1724; found 480.1737 (MH⁺).

Compound 40:1-(Cyanomethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3-dihydro-benzo[b][1,4]dioxin-6-yl)]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 10.45 (s, 1H), 7.05 (d, J=7.8 Hz, 2H), 6.9 (m, 5H),4.75 (d, J=9 Hz, 2H), 4.6 (t, J=7 Hz, 1H), 4.3 (s, 4H), 3.8 (t, J=7 Hz,1H), 3.7 (s, 3H), 3.45 (m, 1H), 3.2 (t, J=7 Hz, 1H), 2.7 (m, 2H), 2.55(m, 1H). Anal. calcd. for C₂₂H₂₄N₄O₆S 0.8H₂O: C, 54.27; H, 5.29; N,11.50; found C, 54.45; H, 5.12; N, 11.25. FAB-HRMS calcd. 473.1495;found 473.1501 (MH⁺).

Compound 41:1-(Cyanomethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-methoxy)-phenyl]-2-imidazolidinone.An alternative name for this compound is1-cyano-N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide.¹H NMR (DMSO-d₆) δ 10.5 (s, 1H), 7.3 (d, J=7.8 Hz, 2H), 6.9 (m, 4H), 6.8(d, J=7.8 Hz, 2H), 4.8 (d, J=9 Hz, 2H), 4.6 (t, J=7 Hz, 1H), 3.9 (m,1H), 3.8 (s, 3H), 3.75 (s, 3H), 3.5 (m, 2H), 3.3 (m, 1H), 2.75 (m, 2H).Anal calcd. for C₂₁H₂₄N₄O₅S: C, 56.74; H, 5.44; N, 12.60; found C,56.91; H, 5.66; N, 12.42. FAB-HRMS calcd. 445.1546; found 445.1562(MH⁺).

Compound 42:1-[(N-3-Pyridinylmethylsulfonyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-difluoromethoxyphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 8.84 (s, 1H), 8.60 (s, 1H), 8.19 (d, J=7.8 Hz, 1H),8.10 (bs, 1H), 7.48 (m, 1H), 7.29 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.7 Hz,2H), 7.08 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 6.56 (t, J=73.8 Hz,1H), 4.51 (s, 2H), 4.48 (m, 1H), 4.00 (t, J=8.1 Hz, 1H), 3.74 (s, 3H),3.72 (m, 1H), 3.43 (t, J=8.1 Hz, 1H), 2.96 (m, 1H), 2.76 (m, 1H), 2.70(m, 1H). MS 533 (MH⁺). Anal. Calcd. for C₂₅H₂₆F₂N₄O₅S: C, 56.38, H,4.92; N, 10.52. Found: C, 56.08, H, 4.82; N, 10.28.

Compound 43:1-[(Phenylmethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethyl-phenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.55 (m, 2H), 7.43 (m, 3H), 7.20 (d, J=7.5 Hz, 1H),7.12 (d, J=8.1 Hz, 2H), 7.04 (m, 2H), 6.86 (m, 3H), 4.48 (t, J=8.4 Hz,1H), 4.44 (s, 2H), 3.99 (t, J=8.4 Hz, 1H), 3.80 (m, 1H), 3.72 (s, 3H),3.36 (t, J=8.4 Hz, 1H), 3.01 (m, 1H), 2.78 (m, 1H), 2.71 (m, 1H), 2.32(s, 6H). MS 494 (MH⁺). Anal. Calcd. for C₂₇H₃₁N₃O₄S: C, 65.70, H, 6.33;N, 8.51. Found: C, 65.45, H, 6.19; N, 8.38.

Example 4 describes the synthesis of exemplary compounds having FormulaXII.1-[3-(4-methoxyphenyl)propyl]-5-[(4-methoxy)-phenyl]-2-imidazolidinonecan be prepared by the procedures described in Examples 1 and 2 hereinabove by substituting 3-(4-methoxyphenyl)propyl amine for2-(4-methoxyphenyl)ethyl amine. The skilled practitioner will know howto substitute the appropriate reagents, starting materials andpurification methods known to those skilled in the art, in order toprepare additional compounds of the present invention.

EXAMPLE 4

Compound 44:1-(Sulfamoylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone.An alternative name for this compound is1-(Aminosulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone.

5-(4-Methoxy-phenyl)-1-[3-(4-methoxy-phenyl)-propyl]-imidazolidin-2-oneand iterations thereof can be prepared by substituting3-(4-methoxyphenyl)propyl amine into step (b) of Examples 1 or 2 asdescribed herein above. The formulator can, for example, without undueexperimentation substitute other 3-(substituted aryl)propyl amines for3-(4-methoxy-phenyl)ethyl amine in order to prepare exemplary analogsencompassed within formula XII, inter alia, 3-(4-tert-butylphenyl)propylamine and 3-(4-methoxyphenyl)-1-methylpropyl amine.

Preparation of1-amino-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone:To a solution of1-[3-(4-methoxyphenyl)propyl]-5-[(4-methoxy)-phenyl]-2-imidazolidinone(0.6 g, 1.75 mmol) in acetic acid (15 mL) is added dropwise a solutionof NaNO₂ (0.12 g, 1.8 mmol) in water (1 mL). The mixture is cooled in anice bath to 5° C. and zinc dust (0.6 g, 9 mmol) is added in portions(starting with 0.5 g addition) over 50 minutes at less than 12° C. Thereaction is stirred for 5 minutes and the ice bath is removed. Thereaction temperature rises quickly to about 20° C. and the reaction ismaintained below about 32° C. with an ice bath. The reaction is stirredfor 70 minutes at 20° C. to 27° C. and any unreacted zinc is removed byfiltration. The volume of the filtrate is reduced in vacuo then dilutedwith dichloromethane (15 mL). To the stirred mixture is addedconcentrated ammonium hydroxide (2 mL), keeping the temperature belowabout 32° C. with an ice bath. The organic phase is separated, washedwith brine, dried (Na₂SO₄), and concentrated to afford 0.68 g(quantitative yield) of the desired compound as a colorless oil which isused without further purification.

Preparation of1-(Sulfamoylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone:To a solution of chlorosulfonylisocyanate (0.175 mL, 2 mmol) in CH₂Cl₂(3 mL) at −30° C. is added dropwise a solution of tert-butanol (150 mg,2 mmol) in CH₂Cl₂ (1 mL). This solution is allowed to warm to 0° C. for3 minutes and then re-cooled to −20° C.1-Amino-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinoneprepared in the above procedure and triethylamine (0.28 mL, 2 mmol) aredissolved in CH₂Cl₂ (2 mL) and this solution is added to the reactionvessel containing the reactive isocyanate intermediate. The combinedingredients are then allowed to warm to room temperature after which thesolvent is removed under reduced pressure and the crude product purifiedover silica (hexane/EtOAc) to afford 0.67 g of a white powder which isdissolved in CH₂Cl₂ (3 mL), cooled to 5° C. and trifluoroacetic acid (1mL) is added. The solution is allowed to warm to room temperature andstir for about 30 minutes after which the solution is concentrated todryness, re-dissolved in CH₂Cl₂, washed with saturated aqueous NaHCO₃and concentrated to afford 0.27 g (32% yield) of the desired product. ¹HNMR (DMSO-d₆) δ 8.5 (s, 1H), 7.3 (d, J=7.8 Hz, 1H), 7.05 (d, J=7.8 Hz,2H), 7.0 (s, 2H), 6.95 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 4.7 (t,J=7 Hz, 1H), 3.9 (t, J=6 Hz, 1H), 3.8 (s, 3H), 3.7 (s, 3H), 3.3 (m, 2H),2.7 (m, 1H), 2.5 (m, 2H), 1.7 (m, 2H). Anal. calcd. for C₂₀H₂₆N₄O₅S0.8H₂O: C, 53.51; H, 6.19; N, 12.48; found C, 53.86; H, 5.98; N, 12.08.FAB-HRMS calcd. 435.1702; found 435.1706 (MH⁺).

The following are non-limiting examples of compounds having Formula XII.

Compound 45:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.23 (m, 6H), 7.11 (m, 3H), 4.56 (t, J=8.1 Hz, 1H),3.94 (t, J=8.1 Hz, 1H), 3.46 (m, 2H), 3.17 (s, 3H), 2.86 (m, 1H), 2.56(t, J=7.8 Hz, 2H), 1.93 (m, 1H), 1.77 (m, 2H), 1.03 (m, 2H), 0.75 (m,2H). MS m/z (ESI, positive): 414 (MH⁺), 436 [M+Na]⁺, (ESI negative): 412[M−H]⁻. Anal Calcd for C₂₂H₂₇N₃O₃S: C, 63.90; H, 6.58; N, 10.16. Found:C, 64.07; H, 6.71; N, 10.22.

Compound 46:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(4-methoxyphenyl)-2-imidazolidinone:¹H-NMR (CDCl₃) δ 7.20 (m, 8H), 6.93 (d, J=8.4 Hz, 2H), 4.55 (t, J=8.1Hz, 1H), 3.94 (t, J=8.4 Hz, 1H), 3.85 (s, 3H), 3.46 (m, 2H), 3.17 (s,3H), 2.86 (m, 1H), 2.56 (t, J=7.8 Hz, 1H), 1.75 (m, 2H). (MS) 404 (MH⁺),402 (M−H⁻). Anal. Calcd for C₂₀H₂₅N₃O₄S: C, 59.53; H, 6.25; N, 10.41.Found: C, 59.90; H, 6.39; N, 10.50.

Compound 47:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.44 (d, J=8.4 Hz, 2H), 7.26 (m, 5H), 7.13 (m, 2H),6.90 (s, 1H), 4.59 (t, J=8.1 Hz, 1H), 3.94 (t, J=8.4 Hz, 1H), 3.48 (m,2H), 3.18 (s, 3H), 2.90 (m, 1H), 2.58 (t, J=7.8 Hz, 2H), 1.76 (m, 2H),1.37 (s, 9H). MS m/z (ESI, positive): 430 (MH⁺). Anal calcd forC₂₃H₃₁N₃O₃S: C, 64.31; H, 7.27; N, 9.78. Found: C, 64.52; H, 7.56; N,9.90.

Compound 48:1-(Methylsulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-cyclopropyl)-phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.45 (s, 1H), 7.25 (d, J=7.8 Hz, 2H), 7.1 (d, J=7.8Hz, 2H), 7.0 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 4.65 (t, J=6 Hz,1H), 3.85 (t, J=6 Hz, 1H), 3.7 (s, 3H), 3.25 (m, 2H), 3.0 (s, 3H), 2.65(m, 1H), 2.4 (m, 2H), 1.95 (m, 1H), 1.6 (m, 2H), 0.9 (m, 2H), 0.7 (m,2H). Anal. calcd. for C₂₃H₂₉N₃O₄S 0.25H₂O: C, 61.65; H, 6.69; N, 9.37;found C, 61.52; H, 6.49; N, 9.35. FAB-HRMS calcd. 444.1957; found444.1955 (MH⁺).

Compound 49:1-(Methylsulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)-phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.5 (s, 1H), 7.3 (d, J=7.8 Hz, 2H), 7.05 (d, J=7.8Hz, 2H), 6.95 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 4.65 (t, J=8.1Hz, 1H), 3.85 (t, J=8.1 Hz, 1H), 3.8 (s, 3H), 3.7, (s, 3H), 3.25 (m,2H), 3.05 (s, 3H), 2.65 (m, 1H), 2.4 (m, 2H), 1.6 (m, 2H). Anal. calcd.for C₂₁H₂₇N₃O₅S 0.25H₂O: C, 57.58; H, 6.32; N, 9.59; found C, 57.73; H,6.26; N, 9.54. FAB-HRMS calcd. 434.1750; found 434.1763. (MH⁺).

Compound 50:1-(Methylsulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-tert-butyl)phenyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 10.2 (s, 1H) 7.5 (d, J=7.8 Hz, 2H), 7.3 (d, J=7.8 Hz,2H), 7.05 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 5.5 (m, 1H), 5.3 (m,1H), 4.6 (t, J=8 Hz, 1H), 3.8 (t, J=8 Hz, 1H), 3.7 (s, 3H), 3.5 (m, 1H),3.3 (t, J=8 Hz, 1H), 2.8-2.6 (m, 2H) 1.3 (s, 9H). FAB-HRMS calcd. forC₂₄H₃₃N₄O₃S: 460.2270; found 460.2275 (MH⁺).

Example 5 describes the synthesis of exemplary compounds having FormulaXIII. The skilled practitioner will know how to substitute theappropriate reagents, starting materials and purification methods knownto those skilled in the art, in order to prepare additional compounds ofthe present invention.

EXAMPLE 5 Compound 51:1-[[2-(Cyclopropylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone

Preparation of 9H-fluoren-9-ylmethyl chlorosulfonylacetate. A solutionof 9-(fluorenyl)methyl alcohol (4.8 g, 0.0245 mol) in dichloromethane(65 mL) is added slowly over 11 minutes to a solution ofchlorosulfonylacetyl chloride (2.6 mL, 0.0245 mol) in dichloromethane(24 mL) at −23° C. to −19° C. The reaction is stirred in an ice bath for6.5 hours, then stirred at ambient temperature for 20 minutes, andconcentrated. The residue is dissolved in diethyl ether (13 mL) andslowly diluted with hexanes (26 mL). The mixture is stirred for 30minutes and the solid which forms is collected by filtration to afford5.96 g (72% yield) of the desired compound. ¹H NMR (CDCl₃) δ 7.81 (d,J=7.5 Hz, 2H), 7.65 (d, J=7.5 Hz, 2H), 7.47 (m, 2H), 7.37 (m, 2H), 4.67(d, J=6.6 Hz, 2H), 4.64 (s, 2H), 4.31 (t, J=12.9 Hz, 1H).

Preparation of1-[[2-(9H-fluoren-9-ylmethoxy)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone.To a solution of1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinonep-toluenesulfonic acid salt (2.61 g, 0.0050 mol), dichloromethane (12mL), and N-methylmorpholine (1.53 mL, 0.014 mol) is added a solution of9H-fluoren-9-ylmethyl chlorosulfonylacetate, 14, (1.76 g, 0.0052 mol) indichloromethane (7 mL) slowly over 7 minutes at 15° C. to 20° C. Thereaction is stirred at ambient temperature for 45 minutes, and thenwashed twice with 0.1 N HCl and water. The organic phase is dried(sodium sulfate) and concentrated to a foamy solid. The residue ispurified over silica (0%-50% ethyl acetate/hexanes gradient) to afford2.1 g of the desired compound. ¹H NMR (CDCl₃) δ 7.81 (d, J=7.5 Hz, 2H),7.69 (d, J=7.5 Hz, 2H), 7.45 (m, 2H), 7.36 (m, 2H), 7.27 (s, 1H), 7.17(m, 2H), 7.10 (m, 2H), 7.02 (m, 2H), 6.82 (m, 2H), 4.63 (m, 2H), 4.45(t, J=8.4 Hz, 1H), 4.35 (m, 3H), 3.94 (t, J=8.4 Hz, 1H), 3.78 (s, 3H),3.65 (m, 1H), 3.38 (t, J=8.1 Hz, 1H), 2.92 (m, 1H), 2.74 (m, 1H), 2.64(m, 1H), 1.94 (m, 1H), 1.03 (m, 2H), 0.74 (m, 2H). MS 652 (MH⁺). Anal.calcd. for C₃₇H₃₇N₃O₆S¾H₂O: C, 66.80; H, 5.83; N, 6.32. Found: C, 66.78;H, 5.72; N, 6.30.

Preparation of[[[4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl]amino]sulfonyl]aceticacid. To a solution of1-[[(9H-fluoren-9-ylmethyloxy)carbonylmethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone(2.0 g, 0.0031 mol) in DMF (15 mL) at room temperature is added1,8-diazabycyclo[5.4.0]undec-7-ene (0.35 mL). The reaction is stirredfor approximately one hour, diluted with ice-cold 0.1 N HCl andextracted with ethyl acetate. The organic phase is washed with brine,dried (sodium sulfate) and concentrated. The residue is warmed inapproximately 20 mL of ether and diluted slowly with approximately 20 mLof hexanes. The liquid is decanted and the resulting material is driedunder vacuum to afford 1.08 g of the desired compound. ¹H NMR (CDCl₃) δ8.03 (bs, 1H), 7.19 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.1 Hz, 2H), 7.05 (m,2H), 6.84 (m, 2H), 4.51 (t, J=8.4 Hz, 1H), 4.30 (s, 2H), 4.01 (t, J=8.7,1H), 3.81 (s, 3H), 3.66 (m, 1H), 3.51 (m, 1H), 2.95 (m, 1H), 2.64 (m,1H), 1.93 (m, 1H), 1.02 (m, 2H), 0.74 (m, 2H). MS 652 (MH⁺). Anal.calcd. for C₂₃H₂₇N₃O₆S¼C₄H₁₀O: C, 58.58; H, 6.04; N, 8.54. Found: C,58.37; H, 6.01; N, 8.35.

Preparation of1-{[2-(cyclopropylamino)-2-oxoethyl]sulfonylamino}-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone.To a solution of[[4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl]-amino]sulfonyl]aceticacid (459 mg, 0.97 mmol) in dichloromethane (20 mL) at 10° C. is addedbenzotriazol-1-yloxytripyrrolidino-phosphonium hexafluorophosphate(PyBOP) (1053 mg, 2.0 mmol), Hunig's base (0.51 mL, 2.9 mmol), andcyclopropylamine (0.20 mL, 2.9 mmol). The reaction is stirred at ambienttemperature for one hour, and is washed with 1.0 N HCl, water, andbrine. The organic phase is dried (sodium sulfate) and concentrated to asolid. The residue is purified over a C18 reverse phase chromatographiccolumn (eluting with 15%-95% acetonitrile/water (0.1% TFA)) to afford289 mg of the desired compound. ¹H NMR (CDCl₃) δ 8.43 (d, J=3.6 Hz, 1H),7.12 (m, 5H), 7.06 (m, 2H), 6.83 (m, 2H), 4.49 (t, J=8.4 Hz, 1H), 4.00(m, 3H), 3.80 (s, 3H), 3.68 (m, 1H), 3.42 (m, 1H), 3.42 (m, 1H), 2.95(m, 1H), 2.86 (m, 1H), 2.72 (m, 1H), 2.65 (m, 1H), 1.93 (m, 1H), 1.01(m, 2H), 0.83 (m, 2H), 0.74 (m, 2H), 0.64 (m, 2H). MS 513 (MH⁺). Anal.calcd. for C₂₆H₃₂N₄O₅S½H₂O: C, 59.87; H, 6.38; N, 10.74. Found: C,59.62; H, 6.14; N, 10.49.

The following are non-limiting examples of compounds having formulaXIII.

Compound 52:1-[(2-Amino-2-oxoethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.86 (d, J=12.9 Hz, 2H), 7.19 (d, J=8.1 Hz, 2H), 7.11(d, J=8.4 Hz, 2H), 7.07 (m, 2H), 6.88 (s, 1H), 6.83 (m, 2H), 4.50 (t,J=8.4 Hz, 1H), 4.11 (m, 2H), 3.99 (t, J=8.4 Hz, 1H), 3.80 (s, 3H), 3.66(m, 1H), 3.48 (m, 1H), 2.94 (m, 1H), 2.75 (m, 1H), 2.64 (m, 1H), 1.94(m, 1H), 1.02 (m, 2H), 0.74 (m, 2H). MS 473 (MH⁺). FAB-HRMS: anal. calcdfor C₂₃H₂₈N₄O₅S: 473.1859. Found: 473.1875.

Compound 53:2-(N-(4-(4-cyclopropylphenyl)-3-(4-methoxyphenethyl)-2-oxoimidazolidin-1-yl)sulfamoyl)-N-(3-hydroxy-3-methylbutan-2-yl)acetamide:¹H NMR (CDCl₃) δ 9.63 (d, J=4.5 Hz, 1H), 8.16 (d, J=8.7 Hz, 1H), 7.26(d, J=8.1 Hz, 2H), 7.14 (J=8.4 Hz, 2H), 7.04 (d, J=8.4 Hz, 2H), 6.83 (d,J=8.7 Hz, 2H), 4.65 (t, J=8.1 Hz, 1H), 4.36 (d, J=5.7 Hz, 1H), 4.03 (m,2H), 3.89 (m, 1H), 3.77 (m, 1H), 3.72 (s, 3H), 3.48 (m, 1H), 3.33 (m,2H), 2.73 (m, 2H), 2.57 (m, 1H), 1.95 (m, 1H), 1.82 (m, 1H), 1.11 (s,3H), 1.08 (s, 3H), 1.07 (s, 1.5H), 1.05 (s, 1.5H), 0.97 (m, 2H), 0.70(m, 2H). MS 559 (MH⁺). FAB-HRMS: anal. calcd for C₂₈H₃₈N₄O₆S: 559.2590.Found: 559.2593.

Compound 54:1-[[2-(Dimethylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.21 (s, 1H), 7.16 (d, J=8.1 Hz, 2H), 7.10 (d, J=8.4Hz, 2H), 7.03 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 4.44 (m, 3H),3.98 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.61 (m, 1H), 3.48 (t, J=8.1 Hz,1H), 3.07 (s, 3H), 3.06 (s, 3H), 2.90 (m, 1H), 2.70 (m, 1H), 2.64 (m,1H), 1.93 (m, 1H), 1.02 (m, 2H), 0.73 (m, 2H). MS 501 (MH⁺). FAB-HRMS:anal. calcd for C₂₅H₃₂N₄O₅S: 501.2172. Found: 501.2175.

Compound 55:1-[[2-(Dimethylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.21 (s, 1H), 7.21 (m, 2H), 7.02 (m, 2H), 6 93 (m, 2H),6 83 (m, 2H), 4.43 (m, 2H), 3.98 (t, J=8.7 Hz, 1H), 3.85 (s, 3H), 3.81(s, 3H), 3.61 (m, 1H), 3.49 (t, J=8.4 Hz, 1H), 3.07 (s, 6H), 2.90 (m,1H), 2.73 (m, 1H), 2.63 (m, 1H). MS 491 (MH⁺). Anal. Calcd. ForC₂₃H₃₀N₄O₆S½H₂O: C, 55.30; H, 6.25; N, 11.21. Found: C, 55.11; H, 6.13;N, 11.12.

Compound 56:1-[[2-(Cyclopropylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.81 (d, J=3.6 Hz, 1H), 7.63 (s, 1H), 7.21 (, J=8.4 Hz,2H), 7.04 (d, J=8.4 Hz, 2H), 6.93 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.4 Hz,2H), 4.50 (t, J=8.7 Hz, 1H), 4.07 (s, 2H), 4.00 (t, J=8.4 Hz, 1H), 3.84(s, 3H), 3.79 (s, 3H), 3.64 (m, 1H), 3.47 (m, 1H), 2.94 (m, 1H), 2.87(m, 1H), 2.71 (m, 1H), 2.64 (m, 1H). MS 503 (MH⁺). FAB-HRMS: anal. calcdfor C₂₄H₃₀N₄O₆S: 503.1964. Found: 503.1956.

Compound 57:1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.33 (m, 1H), 7.22 (m, 2H), 7.07 (m, 2H), 6.95 (m, 2H),6.85 (m, 2H), 4.50 (t, J=8.4 Hz, 1H), 4.07 (s, 2H), 4.00 (t, J=8.4 Hz,1H), 3.86 (s, 3H), 3.80 (s, 3H), 3.68 (m, 1H), 3.45 (m, 1H), 3.24 (m,2H), 2.97 (m, 1H), 2.74 (m, 1H), 2.68 (m, 1H), 1.08 (m, 1H), 0.57 (m,2H), 0.30 (m, 2H). MS 517 (MH⁺). Anal. calcd. for C₂₅H₃₂N₄O₆S¾H₂O: C,56.64; H, 6.37; N, 10.57. Found: C, 56.77; H, 6.07; N, 10.49.

Compound 58:N-(cyclopropylmethyl)-2-(N-(4-(4-cyclopropylphenyl)-3-(4-methoxyphenethyl)-2-oxoimidazolidin-1-yl)sulfamoyl)acetamide.¹H NMR (CDCl₃) δ 8.24 (t, J=4.8 Hz, 1H), 7.16 (d, J=8.4 Hz, 2H), 7.12(d, J=8.4 Hz, 2H), 7.07 (m, 2H), 6.98 (s, 1H), 6.84 (m, 2H), 4.50 (t,J=8.4 Hz, 1H), 4.05 (m, 2H), 4.00 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.71(m, 1H), 3.43 (m, 1H), 3.24 (m, 2H), 2.97 (m, 1H), 2.74 (m, 1H), 2.67(m, 1H), 1.94 (m, 1H), 1.05 (m, 3H), 0.74 (m, 2H), 0.56 (m, 2H), 0.30(m, 2H). MS 527 (MH⁺). Anal. calcd. for C₂₇H₃₄N₄O₅S½H₂O: C, 60.54; H,6.59; N, 10.75. Found: C, 57.69; H, 6.19 N, 10.46.

Compound 59:1-[[2-(Cyclobutylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.47 (d, J=7.2 Hz, 1H), 7.22 (d, J=8.7 Hz, 2H), 7.08(d, J=8.7 Hz, 2H), 6.98 (s, 1H), 6.95 (d, J=8.7 Hz, 2H), 6.84 (d, J=8.4Hz, 2H), 4.48 (m, 2H), 4.01 (m, 3H), 3.86 (s, 3H), 3.80 (s, 3H), 3.71(m, 1H), 3.43 (m, 1H), 2.98 (m, 1H), 2.74 (m, 1H), 2.65 (m, 1H), 2.37(m, 2H), 2.03 (m, 2H), 1.79 (m, 2H). MS 517 (MH⁺). Anal. calcd. forC₂₇H₃₄N₄O₅SH₂O: C, 56.17; H, 6.41; N, 10.48. Found: C, 56.18; H, 6.07 N,10.33.

Compound 60:1-[[2-[(Bis(methoxyethyl)amino)]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.13 (bs, 1H), 7.16 (m, 2H), 7.08 (m, 2H), 7.03 (m,2H), 6.83 (m, 2H), 4.68 (d, J=15.3 Hz, 1H), 4.59 (d, J=15.3 Hz, 1H),4.41 (t, J=8.4 Hz, 1H), 3.96 (t, J=8.4 Hz, 1H), 3.61 (s, 3H), 3.67-3.53(m, 9H), 3.47 (m, 1H), 3.38 (s, 3H), 3.38 (s, 3H), 2.90 (m, 1H), 2.73(m, 1H), 2.64 (m, 1H), 1.93 (m, 1H), 1.02 (m, 2H), 0.73 (m, 2H). MS 589(MH⁺). Anal. calcd. for C₂₉H₄₀N₄O₇S: C, 59.16; H, 6.85; N, 9.52. Found:C, 58.78; H, 6.72; N, 9.55.

The following are non-limiting examples of compounds having Formula XIV.Exemplary compounds having Formula XIV can be prepared according to theprocedures outlined herein above in Example 3 by adjusting theconditions in a manner known to the artisan of ordinary skill.

Compound 61:1-[(Methylsulfonylmethyl)sulfonyl]amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-Cyclopropylphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 8.11 (s, 1H), 7.18 (d, J=8.1 Hz, 2H), 7.10 (d, J=8.1Hz, 2H), 7.05 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.7 Hz, 2H), 4.95 (m, 2H),4.49 (t, J=8.4 Hz, 1H), 3.96 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.70 (m,1H), 3.41 (t, J=8.1 Hz, 1H), 3.26 (s, 3H), 2.93 (m, 1H), 2.65 (m, 2H),1.93 (m, 1H), 1.02 (m, 2H), 0.74 (m, 2H). MS 508 (MH⁺), 506 (MH⁻). Anal.Calcd for C₂₃H₂₉N₃O₆S₂: C, 54.42; H, 5.76; N, 8.28. Found: C, 53.99: h,5.74; N, 7.97.

Example 6 describes the synthesis of exemplary compounds having formulaXV. The skilled practitioner will know how to substitute the appropriatereagents, starting materials and purification methods known to thoseskilled in the art, in order to prepare additional compounds of thepresent invention.

EXAMPLE 6 Compound 62:1-[(Pyridin-3-yl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone

1-[(Pyridin-3-yl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinonetoluenesulfonic acid (0.3 g, 0.58 mmol) is stirred in dichloromethane (6mL) and 3-pyridylsulfonylchloride HCl (135 mg, 0.63 mmol) is addedfollowed by 4-methylmorpholine (0.2 mL). The mixture is heated in amicrowave oven at 80° C. for 25 minutes. The mixture is evaporated andpurified over silica (hexane/ethylacetate) to give the afford 0.12 g(41% yield) of the desired product as a white solid. ¹H NMR (DMSO-d₆) δ10.3 (s, 1H), 9.0 (s, 1H), 8.9 (d, J=6 Hz, 1H), 8.2 (d, J=7.8 Hz, 1H),7.65 (m, 1H), 7.2 (d, J=7.8 Hz, 2H), 7.05, (d, J=7.8 Hz, 2H), 6.95 (d,J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 4.5 (t, J=7 Hz, 1H), 3.8 (s, 3H),3.75 (s, 3H), 3.3 (m, 1H), 3.2 (m, 1H), 2.75 (m, 2H), 2.4 (m, 2H). Anal.calcd. for C₂₄H₂₆N₄O₅S: C, 59.74; H, 5.43; N, 11.61; found C, 59.60; H,5.47; N, 11.37. FAB-HRMS calcd. 483.1702; found 483.1720 (MH⁺).

Compound 63:1-[(Phenylmethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.55 (m, 2H), 7.42 (m, 3H), 7.21 (d, J=8.4 Hz, 2H),7.10 (m, 3H), 6.94 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.1 Hz, 2H), 4.47 (m,3H), 3.97 (t, J=8.3 Hz, 1H), 3.86 (s, 3H), 3.72 (m, 4H), 3.36 (t, J=8.3Hz, 1H), 2.99 (m, 1H), 2.76 (m, 1H), 2.68 (m, 1H). (MS) 496 (MH⁺), 494(M−H⁻). Anal. Calcd for C₂₆H₂₉N₃O₅S: C, 63.01; H, 5.90; N, 8.48. Found:C, 62.57; H, 5.82; N, 8.14.

Compound 64:1-[(Pyridin-3-yl)methanesulfonyl]amino-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-imidazolidin-2-one:¹H-NMR (CDCl₃) δ: 8.78 (s, 1H), 8.54 (d, J=7.8 Hz, 1H), 7.94 (d, J=7.8Hz, 1H), 7.32 (m, 1H), 7.17 (m, 2H), 7.09 (t, J=7.8 Hz, 4H), 6.82 (d,J=8.7 Hz, 2H), 4.48 (m, 3H), 3.98 (t, J=8.4 Hz, 1H), 3.74 (m, 4H), 3.39(t, J=8.4 Hz, 1H), 2.97 (m, 1H), 2.72 (m, 2H), 1.93 (m, 1H), 1.03 (m,2H), 0.74 (m, 2H). MS m/z (ESI, positive): 507 [M+H]⁺. Anal calcd forC₂₇H₃₀N₄O₄S: C, 64.01; H, 5.97; N, 11.06. Found: C, 63.82; H, 5.70; N,11.24.

Compound 65:1-[(Pyridin-3-yl)methylsulfonyl]amino-3-[(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.80 (s, 1H), 8.48 (d, J=4.8 Hz, 1H), 7.92 (d, J=8.1Hz, 1H), 7.19 (m, 6H), 7.06 (d, J=7.8 Hz, 2H), 6.81 (d, J=8.1 Hz, 2H),4.49 (m, 2H), 3.99 (t, J=8.1 Hz, 1H), 3.74 (m, 4H), 3.42 (t, J=8.4 Hz,1H), 2.95 (m, 1H), 2.76 (m, 1H), 2.66 (m, 1H), 2.37 (s, 3H). MS 481(MH⁺), 479 (M−H⁻). Anal. Calcd for C₂₅H₂₈N₄O₄S: C, 62.48; H, 5.87; N,11.66. Found: C, 62.59; H, 6.03; N, 11.54.

Compound 66:1-[(Pyridin-3-yl)methylsulfonyl]amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 8.79 (s, 1H), 8.49 (d, J=4.2 Hz, 1H), 7.92 (d, J=7.8Hz, 1H), 7.28 (m, 1H), 7.19 (dd, J=2.1, 8.7 Hz, 2H), 7.05 (dd, J=2.1,8.4 Hz, 6.90 (dd, J=2.1, 8.7 Hz, 2H), 6.80 (dd, J=2.1, 8.7 Hz, 2H), 4.47(m, 3H), 3.97 (t, J=8.4 Hz, 1H), 3.82 (ss, J=2.1 Hz, 3H), 3.69 (m, 4H),3.40 (t, J=8.4 Hz, 1H), 2.93 (m, 1H), 2.67 (m, 2H). (MS) 497 (MH⁺), 495(M−H⁻). Anal. Calcd for C₂₅H₂₈N₄O₅S: C, 60.47; H, 5.68; N, 11.28. Found:C, 60.59; H, 5.83; N, 11.20.

Example 7 describes the synthesis of exemplary compounds of the presentinvention wherein R³ is —SO₂[C(R^(5a)R^(5b))]_(j)R⁴. The skilledpractitioner will know how to substitute the appropriate reagents,starting materials and purification methods known to those skilled inthe art, in order to prepare additional compounds of the presentinvention.

EXAMPLE 7 Compound 67:1-[(N-methyl-N-benzylsulfonyl)amino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Preparation of1-[(N-methyl-N-benzylsulfonyl)amino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone.A solution of1-[(N-benzylsulfonyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone(500 mg, 1.0 mmol) in dry DMF (5.5 mL) is cooled in an ice bath and 60%NaH in mineral oil (52 mg, 1.3 mmol) is added. The reaction is stirredcold for 15 minutes and methyl iodide (0.082 mL, 1.3 mmol) is added. Theice bath is removed and the reaction is stirred for 30 minutes. Thereaction is diluted with EtOAc, and washed with water and brine. Theorganic phase is dried (Na₂SO₄) and concentrated. The residue ispurified over silica (0% to 60% EtOAc/hexanes gradient) to afford 253 mgof the desired product. ¹H NMR (CDCl₃) δ 7.61 (m, 2H), 7.42 (m, 3H),7.14 (d, J=8.1 Hz, 1H), 7.10 (d, J=8.1 Hz, 3H), 7.01 (bs, 1H), 6.85 (d,J=8.7 Hz, 2H), 4.76-4.30 (m, 3H), 3.95 (m, 0.5H), 3.84-3.66 (m, 4H),3.29 (m, 0.5H), 3.09 (m, 3H), 2.97 (m, 1H), 2.78 (m, 1H), 2.72 (m, 1H),2.31 (s, 6H). MS 508 (MH⁺). Anal. Calcd. For C₂₈H₃₃N₃O₄S: C, 66.25; H,6.55; N, 8.28. Found: C, 66.26; H, 6.44; N, 8.21.

The following are non-limiting examples of compounds of the presentinvention wherein R³ is —SO₂[C(R^(5a)R^(5b))]_(j)R⁴.

Compound 68:1-[(N-Methoxyethyl-N-methylsulfonyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone¹H NMR (CDCl₃) δ 7.26 (d, J=8.1 Hz, 2H), 7.13 (m, 2H), 7.09 (m, 2H),6.83 (m, 2H), 4.65 (m, 1H), 3.90 (t, J=9.0 Hz, 0.5H), 3.84 (t, J=8.4 Hz,0.5H), 3.73 (s, 1.5H), 3.72 (s, 1.5H), 3.67 (m, 2H), 3.48 (m, 2H), 3.40(m, 2H), 3.28 (s, 1.5H), 3.23 (s, 1.5H), 3.18 (s, 1.5H), 3.04 (s, 1.5H),2.66 (m, 2H), 2.56 (m, 1H), 1.94 (m, 1H), 0.97 (m, 2H), 0.70 (m, 2H). MS488 (MH⁺). FAB-HRMS: anal. calcd for C₂₅H₃₃N₃O₅S: 488.2219. Found:488.2213.

Example 8 describes one method of preparing exemplary compounds havingFormula XVII. The skilled practitioner will know how to substitute theappropriate reagents, starting materials and purification methods knownto those skilled in the art, in order to prepare additional compounds ofthe present invention.

EXAMPLE 8 Compound 69:1-(Acetylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Preparation of1-(acetylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethyl-phenyl)-2-imidazolidinone:A solution of compound1-amino-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinonehydrochloride (300 mg, 0.80 mmol) in dichloromethane (3.0 mL) is cooledin an ice bath and triethylamine (0.26 mL, 1.8 mmol) is added, followedby dropwise addition of acetyl chloride (0.068 mL, 0.96 mmol). Thereaction is stirred in the cold for 45 minutes and washed with 0.1 Naqueous HCl, H₂O, 10% aqueous NaHCO₃, and brine. The organic phase isdried (Na₂SO₄) and concentrated under reduced pressure. The residue ispurified over silica (2.5% methanol/dichloromethane) to afford 237 mg(78% yield) of the desired compound. ¹H NMR (CDCl₃) δ 9.18 (s, 1H), 7.12(m, 3H), 7.07 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.4 Hz), 4.41 (t, J=8.4 Hz,1H), 3.91 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.71 (m, 1H), 3.59 (t, J=8.1Hz, 1H), 2.94 (m, 1H), 2.80 (m, 1H), 2.67 (m, 1H), 2.29 (s, 6H), 2.09(s, 3H). MS 382 (MH⁺). Anal. Calcd. For C₂₂H₂₇N₃O₃¼H₂O: C, 68.46, H,7.18; N, 10.89. Found: C, 68.72, H, 6.97; N, 10.85.

The following are non-limiting examples of compounds having FormulaXVII.

Compound 70:{2-Oxo-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-imidazolidin-1-yl}-urea:¹H NMR (CDCl₃) δ 8.87 (bs, 1H), 7.12 (m, 5H), 6.85 (m, 2H), 6.31 (bs,2H), 4.44 (t, J=8.4 Hz, 1H), 3.92 (t, J=8.4 Hz, 1H), 3.81 (s, 3H), 3.66(m, 2H), 2.97 (m, 1H), 2.80 (m, 1H), 2.72 (m, 1H), 2.31 (s, 6H). MS 383(MH⁺). Anal. Calcd. for C₂₁H₂₆N₄O₃H₂O: C, 62.98; H, 7.05; N, 13.99.Found: C, 63.34; H, 6.92; N, 13.66.

Compound 71:1-(Acetylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-tert-butyl)benzyl]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.65 (s, 1H) 7.3 (d, J=7.8 Hz, 2H), 7.15 (d, J=7.8Hz, 2H), 7.0 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 3.75 (m, 2H), 3.7(s, 3H), 3.45 (m, 1H), 3.25 (m, 1H), 3.2-3.0 (m, 3H), 2.65 (m, 1H), 2.6(m, 1H), 2.5 (s, 3H), 1.3 (s, 9H). Anal. calcd. for C₂₅H₃₃N₃O₅: C,70.89; H, 7.85; N, 9.92; found C, 71.12; H, 7.98; N, 9.76. FAB-HRMScalcd. 424.2600; found 424.2615 (MH⁺).

Compound 72: Cyclopropanecarboxylic acidN-{3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-oxo-imidazolidin-1-yl}-amide:¹H NMR (CDCl₃) δ 9.00 (s, 1H), 7.11 (m, 4H), 6.83 (m, 3H), 4.43 (t,J=9.0 Hz, 1H), 3.84 (m, 4H), 3.68 (m, 1H), 3.61 (m, 1H), 2.91 (m, 1H),2.78 (m, 1H), 2.67 (m, 1H), 2.30 (s, 6H), 1.68 (m, 1H), 1.11 (m, 2H),0.86 (m, 2H). MS 408 (MH⁺). Anal. Calcd. For C₂₄H₂₉N₃O₃¼H₂O: C, 69.96,H, 7.22; N, 10.20. Found: C, 70.14, H, 6.83; N, 9.95.

Compound 73:1-Cyclopropanecarbonylamino-4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxy-phenyl)ethyl]-2-imidazolidinone:¹H-NMR (CDCl₃) δ: 7.42 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.1 Hz, 2H), 7.05(d, J=8.4 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 3.87 (t, J=8.4 Hz, 1H), 3.80(s, 3H), 3.64 (m, 2H), 2.95 (m, 1H), 2.80 (m, 1H), 2.66 (m, 1H), 1.70(m, 1H), 1.34 (s, 6H), 1.09 (m, 2H), 0.86 (m, 2H). MS m/z (ESI,positive): 436 [M+H]⁺. Anal Calcd for C₂₆H₃₃N₃O₃: C, 71.70; H, 7.64; N,9.65. Found: C, 71.51; H, 7.84; N, 9.71.

Compound 74:1-(2-Furanoylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.96 (bs, 1H), 7.97 (s, 1H), 7.78 (m, 1H), 7.71 (s,1H), 7.58 (m, 5H), 7.31 (d, J=7.2 Hz, 2H), 7.00 (s, 1H), 4.88 (t, J=8.7Hz, 1H), 4.41 (t, J=7.8 Hz, 1H), 4.29 (s, 3H), 4.21 (m, 1H), 4.09 (m,1H), 3.41 (m, 1H), 3.29 (m, 1H), 3.18 (m, 1H), 2.77 (s, 9H). MS 434(MH⁺). Anal. Calcd. For C₂₅H₂₇N₃O₄¼H₂O: C, 68.56, H, 6.33; N, 9.59.Found: C, 68.74, H, 6.02; N, 9.19.

Compound 75:1-(Benzoylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 9.49 (s, 1H), 7.85 (m, 2H), 7.46 (m, 1H), 7.38 (m, 2H),7.17 (s, 3H), 7.10 (m, 2H), 6.86 (m, 2H), 4.46 (t, J=8.7 Hz, 1H), 3.94(t, J=8.4 Hz, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.68 (m, 1H), 2.94 (m,1H), 2.86 (m, 1H), 2.74 (m, 1H), 2.31 (s, 6H). MS 444 (MH⁺). Anal.Calcd. For C₂₇H₂₉N₃O₃¼H₂O: C, 72.38, H, 6.64; N, 9.38. Found: C, 72.51,H, 6.09; N, 9.16. FAB-HRMS: anal. Calcd for C₂₇H₂₉N₃O₃: 444.2287. Found:444.2298.

Compound 76:N-{3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-oxo-imidazolidin-1-yl}-2-phenoxyacetamide:¹H NMR (CDCl₃) δ 8.45 (s, 1H), 7.37 (t, J=6 Hz, 2H), 7.16 (d, J=7.5 Hz,1H), 7.08 (m, 5H), 6.99 (m, 2H), 6.84 (d, J=8.4 Hz, 2H), 4.65 (s, 2H),4.38 (t, J=8.1 Hz, 1H), 3.90 (t, J=8.1 Hz, 1H), 3.82 (s, 3H), 3.76 (m,1H), 3.53 (t, J=8.1 Hz, 1H), 2.94 (m, 1H), 2.84 (m, 1H), 2.70 (m, 1H),2.30 (s, 6H). MS 474 (MH⁺). Anal. Calcd. For C₂₈H₃₁N₃O₄: C, 71.01, H,6.60; N, 8.87. Found: C, 70.68, H, 6.46; N, 8.67.

Compound 77:N-{3-[2-(4-Methoxyphenyl)ethyl]-4-[(3,4-dimethylphenyl)]-2-oxo-imidazolidin-1-yl}-2-phenylacetamide:¹H NMR (CDCl₃) δ 9.49 (s, 1H), 7.85 (m, 2H), 7.46 (m, 1H), 7.35 (m, 2H),7.17 (s, 3H), 7.10 (m, 2H), 6.86 (m, 2H), 4.46 (t, J=8.7 Hz, 1H), 3.94(t, J=8.4 Hz, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.68 (t, J=8.1 Hz, 1H),2.94 (m, 1H), 2.86 (m, 1H), 2.74 (m, 1H), 2.31 (s, 6H). MS 444 (MH⁺).Anal. Calcd. For C₂₇H₂₉N₃O₃¼H₂O: C, 72.38, H, 6.64; N, 9.38. Found: C,72.43, H, 6.08; N, 9.18. FAB-HRMS: anal. Calcd for C₂₇H₂₉N₃O₃: 444.2287.Found: 444.2298.

Compound 78:1-(Isoxazol-5-ylcarbonylamino)-3-[2-(4-methoxyphenyl)-ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H-NMR (CDCl₃): δ 9.90 (s, 1H), 8.31 (s, 1H), 7.09 (m, 6H), 6.84 (d,J=8.4 Hz, 2H), 4.46 (t, J=8.4 Hz, 1H), 3.94 (t, J=8.4 Hz, 1H), 3.80 (s,3H), 3.69 (m, 5H), 2.98 (m, 1H), 2.82 (m, 1H), 2.70 (m, 1H), 2.29 (s,6H). MS m/z (ESI, positive): 435 [M+H]⁺, (ESI negative): 433 [M−H]⁻.Anal Calcd for C₂₄H₂₆N₄O₄: C, 66.34; H, 6.03; N, 12.89. Found: C, 66.62;H, 5.80; N, 13.04.

Compound 79:1-(Isoxazol-5-ylcarbonylamino)-3-[2-(4-methoxyphenyl)-ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H-NMR (CDCl₃): δ 9.78 (s, 1H), 8.32 (d, J=1.8 Hz, 1H), 7.42 (d, J=8.4Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.01 (d, J=1.8 Hz, 1H), 6.84 (d, J=8.4Hz, 2H), 4.49 (t, J=8.4 Hz, 1H), 3.96 (t, J=8.4 Hz, 1H), 3.80 (s, 3H),3.67 (m, 2H), 3.00 (m, 1H), 2.84 (m, 1H), 2.68 (m, 1H), 1.34 (s, 9H). MSm/z (ESI, positive): 463 [M+H]⁺, (ESI negative): 461 [M−H]⁻. Anal Calcdfor C₂₆H₃₀N₄O₄: C, 67.51; H, 6.54; N, 12.11. Found: C, 67.80; H, 6.26;N, 12.31.

Compound 80:1-(Methoxycarbonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.21 (d, J=7.8 Hz, 2H), 7.06 (m, 4H), 6.98 (bs, 1H),6.85 (m, 2H), 4.34 (t, J=8.4 Hz, 1H), 3.83 (m, 1H), 3.81 (s, 6H), 3.68(m, 1H), 3.48 (m, 1H), 2.89 (m, 1H), 2.78 (m, 1H), 2.67 (m, 1H), 1.92(m, 1H), 1.01 (m, 2H), 0.73 (m, 2H). MS 410 (MH⁺). Anal. Calcd. forC₂₃H₂₇N₃O₄¼H₂O: C, 66.73; H, 6.70; N, 10.15. Found: C, 66.81; H, 6.62;N, 10.12.

Compound 81:2-(Benzylmethylamino)-N-{4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)-ethyl]-2-oxo-imidazolidin-1-yl}-acetamide:¹H-NMR (CDCl₃): δ 8.73 (s, 1H), 7.36 (m, 8H), 7.07 (d, J=8.4 Hz, 2H),6.83 (d, J=8.7 Hz, 2H), 4.39 (t, J=8.1 Hz, 1H), 3.83 (m, 4H), 3.69 (m,3H), 3.48 (t, J=7.8 Hz, 2H), 3.21 (m, 2H), 2.87 (m, 2H), 2.65 (m, 1H),2.42 (s, 3H), 1.35 (s, 9H). MS m/z (ESI, positive): 529 [M+H]⁺. AnalCalcd for C₃₂H₄₀N₄O₃: C, 72.70; H, 7.63; N, 10.60. Found: C, 72.61; H,7.80; N, 10.65.

Compound 82:N-(4-(4-cyclopropylphenyl)-3-(4-methoxyphenethyl)-2-oxoimidazolidin-1-yl)-2-(N,N-dimethylsulfamoyl)acetamide.¹H NMR (CDCl₃) δ 8.92 (s, 0.5H), 8.31 (s, 0.5H), 7.19 (m, 2H), 7.08 (m,2H), 7.03 (d, J=8.4 Hz, 2H), 6.82 (m, 2H), 4.44 (s, 1H), 4.42 (m, 1H),4.03 (s, 1H), 3.98 (t, J=8.7 Hz, 0.5H), 3.88 (t, J=8.4 Hz, 0.5H), 3.80(s, 3H), 3.62 (m, 1H), 3.50 (m, 1H), 3.08 (s, 1.5H), 3.06 (s, 1.5H),2.99 (s, 3H), 2.90 (m, 1H), 2.72 (m, 1H), 2.63 (m, 1H), 1.92 (m, 1H),1.01 (m, 2H), 0.73 (m, 2H). MS 501 (MH⁺). FAB-HRMS: anal. calcd forC₂₅H₃₂N₄O₅S: 501.2172. Found: 501.2161.

Examples 9 and 10 describe additional methods for preparing exemplarycompounds which have Formula XVII. The skilled practitioner will knowhow to substitute the appropriate reagents, starting materials andpurification methods known to those skilled in the art, in order toprepare additional compounds of the present invention.

EXAMPLE 9 Compound 83:1-[(4-Cyanophenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Preparation of1-[(4-cyanophenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:To a solution of1-amino-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinonehydrochloride (350 mg, 0.93 mmol), THF (4.5 mL), and 4-cyanobenzaldehyde(131 mg, 1.0 mmol) is stirred at 50° C. for 30 minutes, then cooled inan ice bath and glacial acetic acid (3.5 mL) is added. To the resultingmixture is added NaCNBH₃ (183 mg, 2.9 mmol). The reaction is stirred inthe cold for 2 hours and ethyl acetate and H₂O are added. The mixture ismade basic with solid NaHCO₃, and the organic phase is washed with 10%aqueous NaHCO₃ and brine. The organic phase is dried (Na₂SO₄) andconcentrated under reduced pressure. The residue is purified over silica(45% ethyl acetate/hexanes) to afford 167 mg (40% yield) of the desiredproduct. ¹H NMR (CDCl₃) δ 7.65 (m, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.12 (d,J=7.8 Hz, 1H), 7.05 (m, 2H), 6.89 (m, 2H), 6.84 (m, 2H), 4.20 (m, 3H),3.82 (s, 3H), 3.67 (m, 1H), 3.48 (t, J n=8.4 Hz, 1H), 3.06 (t, J=8.1 Hz,1H), 2.91 (m, 1H), 2.76 (m, 1H), 2.67 (m, 1H), 2.29 (s, 3H), 2.26 (s,3H). MS 455 (MH⁺). Anal. Calcd. For C₂₈H₃₀N₄O₂: C, 73.98, H, 6.65; N,12.33. Found: C, 73.68, H, 6.65; N, 12.08.

EXAMPLE 10 Compound 84:4-(3,4-Dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-[(pyridin-4-ylmethyl)amino]-imidazolidin-2-one

Compound 85:{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-carbamicacid tert-butyl ester

Preparation of{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-carbamicacid tert-butyl ester: To a solution of1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinonehydrochloride (500 mg, 1.3 mmol) in CH₂Cl₂ (2.0 mL) is added Hunig'sbase (0.28 mL, 1.6 mmol), followed by a solution ofdi-tert-butyldicarbonate (312 mg, 1.4 mmol) in CH₂Cl₂ (1.0 mL). Thesolution is stirred for 18 hours and washed with 0.1 N aqueous HCl (2×)and 10% aqueous NaHCO₃. The organic phase is dried (Na₂SO₄) andconcentrated. The residue is triturated in hexanes, cooled briefly at−20° C., the solvent decanted and the resulting solid collected toafford 500 mg (87% yield) of the desired compound. ¹H NMR (CDCl₃) δ 7.16(d, J=8.4 Hz, 1H), 7.05 (m, 4H), 6.82 (m, 2H), 4.35 (t, J=8.4 Hz, 1H),3.80 (s, 3H), 3.70 (m, 2H), 3.46 (m, 1H), 2.89 (m, 1H), 2.75 (m, 1H),2.67 (m, 1H), 2.29 (s, 6H), 1.53 (s, 9H). MS 440 (MH⁺). Anal. calcd. forC₂₅H₃₃N₃O₄: C, 68.31, H, 7.57; N, 9.56. Found: C, 68.09, H, 7.48; N,9.24.

Preparation ofN-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-3,3-dimethyl-N-pyridin-4-ylmethylbutyramide:A mixture of{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-carbamicacid tert-butyl ester (459 mg, 1.04 mmol), 4-picolyl chloridehydrochloride (257 mg, 1.57 mmol), and DMF (5.5 mL) is cooled in an icebath and 60% NaH in mineral oil (165 mg, 4.13 mmol) is added. Thereaction is stirred in the ice bath for 3 hours and quenched withice/water. The resulting mixture is extracted with ethyl acetate and theethyl acetate layer is washed with pH 5.8 phosphate buffer and brine.The organic phase is dried (Na₂SO₄) and concentrated under reducedpressure. The crude product is purified over silica (80% ethylacetate/hexanes) to afford 210 mg (38% yield) of the desired compoundwhich is used directly for the next step. MS 531 (MH⁺).

Preparation of4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-[(pyridin-4-ylmethyl)amino]-imidazolidin-2-one:A solution ofN-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-3,3-dimethyl-N-pyridin-4-ylmethyl-butyramide(205 mg, 0.386 mmol) in CH₂Cl₂ (1.5 mL) is cooled in an ice bath andtriethylsilane (0.129 mL, 0.81 mmol) is added, followed bytrifluoroacetic acid (1.5 mL). The ice bath is removed and the reactionis stirred at ambient temperature for 2.5 hours. The reaction isconcentrated to an oil, dissolved in ethyl acetate, and washed with 10%aqueous NaHCO₃, and brine. The organic phase is dried (Na₂SO₄), treatedwith 2N HCl/ether (0.7 mL), and concentrated under reduced pressure. Thesolid which results is re-crystallized from dichloromethane/ether toafford 174 mg (76% yield) of the desired compound. ¹H NMR (DMSO-d₆) δ8.92 (d, J=6.0 Hz, 2H), 8.21 (d, J=6.0 Hz, 2H), 7.14 (d, J=7.5 Hz, 1H),7.00 (m, 4H), 6.82 (d, J=8.1 Hz, 2H), 4.38 (m, 3H), 3.74 (s, 3H), 3.72(m, 1H), 3.44 (m, 1H), 3.14 (t, J=7.8 Hz, 1H), 2.68 (m, 1H), 2.52 (m,1H), 2.24 (s, 3H), 2.20 (s, 3H). MS 431 (MH⁺). Anal. calcd. forC₂₆H₃₀N₄O₂2HCl: C, 62.03, H, 6.41; N, 11.13. Found: C, 61.99, H, 6.41;N, 11.13.

The following are non-limiting examples of compounds which have formulaIV.

Compound 86:1-(Cyclopropylmethylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H-NMR (CDCl₃) δ: 7.53 (s, 2H), 7.15 (d, J=7.5 Hz, 1H), 7.03 (m, 4H),6.82 (d, J=8.7 Hz, 2H), 4.32 (t, J=8.1 Hz, 1H), 3.84 (t, J=8.1 Hz, 1H),3.80 (s, 3H), 3.68 (m, 1H), 3.38 (t, J=8.1 Hz, 1H), 2.95 (m, 3H), 2.69(m, 2H), 2.28 (s, 6H), 1.05 (m, 1H), 0.58 (m, 2H), 0.32 (m, 2H). Analcalcd for C₂₆H₃₂F₃N₃O₄: C, 61.53; H, 6.35; N, 8.28. Found: C, 61.89; H,6.57; N, 8.04.

Compound 87:1-Benzylamino-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H-NMR (CDCl₃) δ: 7.39 (m, 6H), 7.11 (d, J=8.1 Hz, 2H), 7.04 (d, J=8.4Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 5.35 (s, 2H), 4.24 (t, J=8.1 Hz, 1H),4.17 (d, J=3.3 Hz, 1H), 3.81 (s, 3H), 3.66 (m, 1H), 3.53 (t, J=8.1 Hz,1H), 3.13 (t, J=8.1 Hz, 1H), 2.79 (m, 3H), 1.37 (s, 9H). MS m/z (ESI,positive): 458 [M+H]⁺. Anal calcd for C₃₁H₃₅F₃N₃O₃: C, 67.13; H, 6.36;N, 7.58. Found: C, 67.40; H, 6.09; N, 7.76.

Compound 88:1-Benzylamino-4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone:¹H-NMR (CDCl₃) δ: 7.44 (d, J=8.4 Hz, 1H), 7.34 (m, 3H), 7.11 (d, J=7.2Hz, 1H), 7.04 (d, J=8.7 Hz, 2H), 6.89 (m, 5H), 4.18 (m, 3H), 3.81 (s,3H), 3.66 (m, 1H), 3.53 (t, J=8.4 Hz, 1H), 3.12 (t, J=8.1 Hz, 1H), 2.91(m, 1H), 2.70 (m, 2H), 2.27 (d, J=5.4 Hz, 6H). MS m/z (ESI, positive):430 [M+H]⁺. Anal calcd for C₂₉H₃₂F₃N₃O₄: C, 66.15; H, 5.93; F, 10.82; N,7.98. Found: C, 66.50; H, 6.09; F, 11.13; N, 8.21.

Compound 89:1-[(4-Fluorophenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.38 (m, 2H), 7.12 (d, J=7.5 Hz, 1H), 7.05 (m, 4H),6.93 (m, 2H), 6.83 (m, 2H), 4.20 (t, J=8.1 Hz, 1H), 4.14 (d, J=12.3 Hz,1H), 4.08 (d, J=12.6 Hz, H), 3.81 (s, 3H), 3.68 (m, 1H), 3.48 (t, J=8.4Hz, 1H), 2.93 (m, 1H), 2.76 (m, 1H), 2.68 (m, 1H), 2.29 (s, 3H), 2.27(s, 3H). MS 448 (MH⁺). Anal. calcd. For C₂₇H₃₀FN₃O₂: C, 72.46, H, 6.76;N, 9.39. Found: C, 72.36, H, 6.42; N, 9.12.

Compound 90:1-[(4-(Dimethylamino)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 7.47 (d, J=7.8 Hz, 2H), 7.22 (d, J=8.4 Hz, 4H), 6.98(m, 5H), 6.82 (d, J=8.4 Hz, 2H), 4.55 (t, J=7.8 Hz, 1H), 4.25 (d, J=13.2Hz, 1H), 4.19 (d, J=13.2 Hz, 1H), 3.81 (m, 1H), 3.77 (s, 3H), 3.71 (s,3H), 3.43 (m, 1H), 3.30 t, J=7.8 Hz, 1H), 3.04 (m, 1H), 3.01 (s, 6H),2.68 (m, 2H). MS 475 (MH⁺). Anal. calcd. for C₂₈H₃₄N₄O₃½HCl: C, 63.54;H, 6.76; N, 10.59. Found: C, 63.19; H, 6.65; N, 10.30.

Compound 91:1-[(4-(Dimethylamino)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.90 (s, 4H), 7.37 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.1Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.7 Hz, 2H), 4.68 (m, 2H),4.37 (t, J=8.1 Hz, 1H), 3.98 (t, J=7.8 Hz, 1H), 3.78 (m, 4H), 3.60 (m,1H), 3.16 (s, 6H), 2.72 (m, 3H), 1.29 (s, 9H). MS m/z (ESI, positive):501 (MH⁺). Anal calcd for C₃₁H₄₂Cl₂N₄O₂: C, 64.91; H, 7.38; N, 9.77.Found: C, 65.24; H, 7.71; N, 10.02.

Compound 92:1-[(4-(Dimethylamino)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.52 (d, J=7.8 Hz, 2H), 7.33 (bs, 2H), 7.16 (d, J=7.8Hz, 4H), 6.82 (d, J, 8.4 Hz, 2H), 4.53 (t, J=7.8 Hz, 1H), 4.27 (d,J=13.5 Hz, 1H), 4.22 (d, J=13.5 Hz, 1H), 3.84 (t, J=8.1 Hz, 1H), 3.71(s, 3H), 3.50 (m, 1H), 3.34 (t, J=7.5 Hz, 1H), 3.07 (m, 1H), 3.03 (s,6H), 2.73 (m, 1H), 2.64 (m, 1H), 2.23 (s, 3H), 2.21 (s, 3H). MS 473(MH⁺). Anal. calcd. For C₂₉H₃₆N₄O₂2HCl: C, 63.85, H, 7.02; N, 10.27.Found: C, 64.18, H, 6.78; N, 10.07.

Compound 93:1-[(Pyridin-2-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.78 (s, 1H), 8.43 (m, 2H), 7.89 (bs, 3H), 7.08 (d,J=7.5 Hz, 1H), 6.96 (m, 4H), 6.74 (d, J=8.1 Hz, 2H), 4.86 (s, 2H), 4.41(m, 1H), 4.10 (m, 1H), 3.76 (s, 3H), 3.56 (m, 1H), 3.42 (m, 1H), 2.84(m, 1H), 2.61 (m, 1H), 2.53 (m, 1H), 2.24 (s, 3H), 2.23 (s, 3H). MS 431(MH⁺). Anal. calcd. for C₂₆H₃₀N₄O₂2HCl H₂O: C, 59.89, H, 6.58; N, 10.74.Found: C, 59.73, H, 6.62; N, 10.48.

Compound 94:1-[(Pyridin-3-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆+1% TFA-d) δ 9.07 (s, 1H), 8.91 (d, J=5.7 Hz, 1H), 8.67(d, J=8.1 Hz, 1H), 8.10 (dd, J=5.7, 7.8 Hz, 1H), 7.13 (d, J=7.5 Hz, 1H),6.95 (m, 4H), 6.79 (d, J=8.4 Hz, 2H), 4.37 (t, J=8.1 Hz, 1H), 4.27 (s,2H), 3.71 (s, 3H), 3.69 (m, 1H), 3.42 (m, 1H), 3.13 (t, J=7.8 Hz, 1H),2.69 (m, 1H), 2.58 (m, 1H), 2.46 (m, 1H), 2.21 (s, 3H), 2.19 (s, 3H).).MS 431 (MH⁺). Anal. calcd. for C₂₆H₃₀N₄O₂2HCl 3H₂O: C, 56.01, H, 6.87,N, 10.05. Found: C, 56.19, H, 6.47; N, 9.81.

Compound 95:1-[(Pyridin-4-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-(tert-butyl)phenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 8.89 (d, J=6.3 Hz, 2H), 8.17 (d, J=6.6 Hz, 2H), 7.39(2H, J=8.4 Hz, 2H), 7.18 (d, J=8.1 Hz, 2H), 6.98 (d, J=8.4 Hz, 2H), 6.78(d, J=8.7 Hz, 2H), 4.39 (t, J=8.1 Hz, 1H), 4.34 (s, 2H), 3.71 (s, 3H),3.69 (m, 1H), 3.43 (m, 1H), 3.12 (m, 1H), 2.72 (m, 1H), 2.49 (m, 1H),1.29 (s, 9H). MS 459 (MH⁺). Anal. Calcd. For C₂₈H₃₄N₄O₂2HCl½H₂O: C,62.22; H, 6.90; N, 10.37. Found: C, 62.54; H, 6.69; N, 10.18.

For the following compound, the starting material,3-chloromethylquinoline hydrochloride, is prepared according to themethod of J. Am. Chem. Soc. (1955), Vol. 77, 1054-1055, included hereinby reference.

Compound 96:4-(3,4-Dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-[(quinolin-3-ylmethyl)-amino]-2-imidazolidinone:¹H NMR (DMSO-d₆) δ 9.44 (d, J=1.5 Hz, 1H), 9.19 (s, 1H), 8.49 (d, J=8.4Hz, 1H), 8.34 (d, J=8.1 Hz, 1H), 8.16 (t, J=7.2 Hz, 1H), 7.98 (t, J=7.5Hz, 1H), 7.09 (d, J=7.8 Hz, 1H), 6.92 (m, 4H), 6.74 (d, J=8.7 Hz, 2H),4.45 (s, 2H), 4.40 (t, J=8.1 Hz, 1H), 3.79 (t, J=8.1 Hz, 1H), 3.67 (s,3H), 3.40 (m, 1H), 3.24 (t, J=7.8 Hz, 1H), 2.65 (m, 1H), 2.58 (m, 1H),2.40 (m, 1H), 2.19 (s, 3H), 2.13 (s, 3H). MS 481 (MH⁺). FAB-HRMS: anal.calcd for C₃₀H₃₂N₄O₂: 481.2604. Found: 481.2583.

Compound 97:1-[(Phenylethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 7.34 (m, 2H), 7.28 (m, 3H), 7.21 (d, J=7.8 Hz, 1H),7.12 (m, 2H), 7.05 (m, 2H), 6.84 (m, 2H), 4.60 (t, J=8.1 Hz, 1H), 3.88(t, J=8.1 Hz, 1H), 3.70 (s, 3H), 3.52 (m, 1H), 3.31 (m, 3H), 2.88 (m,2H), 2.78 (m, 1H), 2.65 (m, 1H), 2.56 (m, 1H, overlap with DMSO), 2.25(s, 6H). MS 444 (MH⁺). FAB-HRMS: anal. calcd for C₂₈H₃₃N₃O₂: 444.2651.Found: 444.2636.

Compound 98:1-[(4-(1H-imidazol-1-yl)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone:¹H NMR (DMSO-d₆+1% TFA) δ 9.85 (s, 1H), 8.39 (d, J=1.5 Hz, H), 8/01 (d,J=1.8 Hz, H), 7.91 (d, J=8.7 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H), 7.19 (d,J=7.2 Hz, 1H), 7.06 (m, 4H), 7.84 (d, J=7.5 Hz, 2H), 4.60 (t, J=7.5 Hz,1H), 4.47 (m, 2H), 3.72 (s, 3H), 3.54 (m, 1H), 2.79 (m, 1H), 2.65 (m,1H), 2.58 (m, 1H, overlap with DMSO), 2.25 (s, 3H), 2.23 (s, 3H). MS 496(MH⁺). Anal. Calcd. For C₃₀H₃₃N₅O₂2HCl½H₂O: C, 62.39, H, 6.28; N, 12.13.Found: C, 62.72, H, 6.27; N, 11.75.

The following are non-limiting examples of compounds according to thepresent invention.

Compound 99:1-N-[2-(Imidazol-1-yl)ethyl]-N-[iso-butyroyl]amino-3-[2-(4-methoxyphenyl)-ethyl]-4-[(4-tert-butyl)phenyl]-2-imidazolidinone.¹H NMR (DMSO-d₆) 7.8 (brd, 1H), 7.6 (brd, 1H), 7.4 (brm, 4H), 7.25 (brd,1H), 7.1 (brd, 2H), 6.9 (brd, 2H), 4.4 (m, 2H), 4.0 (m, 2H), 3.75 (s,3H), 3.7 (m, 4H), 2.8-2.4 (m, 3H), 1.3 (brs, 15H). FAB-HRMS calcd. forC₃₁H₄₁N₅O₃: 532.3288; found 532.3267 (MH⁺).

Compound 100:1-N-[2-(Imidazol-1-yl)ethyl]-N-[acetyl]amino-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-tert-butyl)phenyl]-2-imidazolidinone.¹H NMR (DMSO-d₆) δ 7.6 (brs, 1H), 7.45 (brm, 3H), 7.33-7.2 (brm, 2H),7.05 (brm, 2H), 6.8 (brm, 3H), 4.6 (brm, 1H), 4.3-4.0 (brm, 2H), 3.8(brm, 1H), 3.65 (s, 3H), 3.5 (brm, 2H), 3.3 (brm, 3H), 2.8-2.6 (brm,2H), 1.8 (m, 3H) 1.3 (s, 9H). FAB-HRMS calcd. for C₂₉H₃₇N₅O₃: 504.2975;found 504.2959 (MH⁺).

Compound 101:1-[(Pyridin-3-yl)methylsulfonyl]amino-3-(3-phenylpropyl)-4-(4-methoxyphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.84 (d, J=1.5 Hz, 1H), 8.47 (dd, J=1.2, 3.6 Hz, 1H),7.95 (dt, J=1.8, 7.8 Hz, 1H), 7.23 (m, 6H), 7.11 (d, J=8.4 Hz, 2H), 6.92(d, J=8.4 Hz, 2H), 4.60 (s, 2H), 4.54 (t, J=8.4 Hz, 1H), 3.97 (m, 1H),3.83 (s, 3H), 3.46 (m, 2H), 2.86 (m, 1H), 2.56 M, 2H), 1.74 (m, 2H).(MS) 481 (MH⁺), 479 (M−H⁻). Anal. Calcd for C₂₅H₂₈N₄O₄S: C, 62.48; H,5.87; N, 11.66. Found: C, 62.89; H, 5.93; N, 11.58.

Compound 102:1-[[2-(9H-fluoren-9-ylmethoxy)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone.HPLC retention time 6.011 minutes, (MS) 652 (MH⁺).

Compound 103:N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-3,3-dimethyl-N-pyridin-4-ylmethylbutyramide.

Compound 104:1-[(2-Amino-2-oxoethyl)sulfonylamino]-3-[3-(4-methoxyphenyl)propyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone:¹H NMR (CDCl₃) δ 8.82 (s, 1H), 8.67 (s, 1H), 7.21 (d, J=8.1 Hz, 2H),7.10 (d, J=8.1 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.81 (d, J=8.7 Hz, 2H),6.60 (s, 1H), 4.57 (t, J=8.1 Hz, 1H), 4.18 (m, 2H), 3.98 (t, J=8.7 Hz,1H), 3.80 (s, 3H), 3.54 (m, 1H), 3.41 (m, 1H), 2.82 (m, 1H), 2.49 (m,2H), 1.93 (m, 1H), 1.70 (m, 2H), 1.03 (m, 2H), 0.73 (m, 2H). MS 487(MH⁺). Anal. calcd. for C₂₄H₃₀N₄O₅S¾H₂O: C, 57.64; H, 6.35; N, 11.20.Found: C, 57.73; H, 6.11; N, 10.91.

Enantio-Selective Synthesis

The compounds of the present invention can be prepared in enhancedenantiomeric purity by preparing the 1-N-amino-2-imidazolidinoneintermediates utilizing the process outlined in Schemes I and Example 11herein below. Example 12 exemplifies a procedure for converting chiralcompounds to Kv1.5 potassium channel inhibitors of the present inventionhaving enhanced enantiomeric purity. What is meant herein by the term“enhanced enantiomeric purity” is a final product wherein the final2-oxazolidinone formed in step (c) of the present process has at least90% of the material isolated existing as one optical isomer; either theR or S enantiomer. In many instances, the optical purity is at least 95%one optical isomer, and in the procedure described herein below inExample 11, 99.5% of the material isolated had the R configuration.However, by using procedures known to the artisan, the optical purity ofthe products formed in step (c) can be further enhanced in theirenantiomeric purity.

Scheme I

The following is a first iteration of the procedure for preparingexemplary compounds of the present invention having enhancedenantiomeric purity. The units R, R¹, and L are the same as definedherein above.

-   -   a) (i) reacting a chiral 2-aminoamide having the formula:    -    with an acid chloride having the formula:    -    L² is a unit having the formula —[C(R^(9a)R^(9b))]_(j)—, the        index j is 1 or 2; in the presence of a base to form a chiral        di-amide having the formula:    -   b) reacting the chiral di-amide formed in step (a) with a        reducing agent to form a di-amine having the formula:    -   c) reacting the di-amine formed in step (b) with a reagent which        is capable of introducing a carbonyl group to form a        2-imidazolidinone having the formula:    -    wherein said 2-imidazolidinone has at least 90% of the same        configuration as the chiral 2-aminoamide of step (a); and    -   d) reacting the 2-imidazolidinone formed in step (c) with a        reagent capable of introducing an amino unit onto the        imidazolidinone ring to form a 1-N-amino-2-imidazolidinone.

Or in a second iteration of the present process, step (a)(i) can besuitably modified to be replaced by the following:

-   -   a)(ii) reacting a chiral 2-aminoamide having the formula:    -    with an acid having the formula:    -    L² is a unit having the formula —[C(R^(9a)R^(9b))]_(j)—, the        index j is 1 or 2; in the presence of a peptide coupling reagent        to form a chiral di-amide having the formula:

The following is a description of the steps comprising the process ofthe present invention.

Step (a) Formation of a chiral di-amide having the formula:

Step (a)(i) is the first iteration of the process of the presentinvention and relates to the coupling of a 2-aminoamide and an acidchloride to form a chiral di-amide.

This step may optionally be conducted in the presence of a solvent whichdoes not react with the either the acid chloride or the 2-aminoamide.Non-limiting examples of said solvents include solvents chosen fromdimethylformamide, dimethylacetamide, tetrahydrofuran,methylenechloride, chloroform, 1,2-dichloroethane,1,1,1-trichloroethane, 1,2-dimethoxyethane, tert-butyl methyl ether,2-methyltetrahydrofuran, diethylene glycol dimethyl ether, dioxane, anddimethylsulfoxide. In another iteration, water can be used as aco-solvent for this reaction under certain known to the artisanconditions.

Step (a)(i) is conducted in the presence of a base. As a first iterationof step (a)(i), non limiting examples of bases which can be used in theprocess of the present invention include bases chosen fromtriethylamine, N-methylmorpholine, diisopropylmethylamine,diisopropyl-ethylamine, pyridine, lutidine, and N-methylpiperidine. In asecond iteration of step (a)(i), and in certain conditions wherein wateris present as a co-solvent, non limiting examples of bases which can beused in the process of the present invention include bases chosen fromsodium bicarbonate, sodium carbonate, sodium hydroxide, potassiumcarbonate, and potassium hydroxide.

Step (a)(ii) is a second iteration of the process of the presentinvention and relates to the coupling of a 2-aminoamide and an acid inthe presence of a peptide coupling reagent to form a chiral di-amide.

The coupling reagents which can be utilized for this step are those wellknown by the artisan, and which include the following non-limitingexamples:

-   -   i) Benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium        hexafluorophosphate (BOP);    -   ii) N,N′-Carbonyldiimidazole (CDI);    -   iii) Dicyclohexylcarbodiimide (DCC);    -   iv) 3-(Diethoxyphosphoryloxy)-3H-benzo[d][1,2,3]triazin-4-one        (DEPBT);    -   v) N,N′-Diisopropylcarbodiimide (DIC);    -   vi) 1-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride        (EDC);    -   vii) 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium        hexafluorophosphate Methanaminium; HATU);    -   viii)        O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate        (HBTU);    -   ix) 1H-Benzotriazolium        1-[bis(dimethylamino)methylene]-5-chloro-hexa-fluorophosphate        (1-),3-oxide (HCTU);    -   x) Benzotriazol-1-yl-oxytripyrrolidinophosphonium        hexafluorophosphate (PyBOP);    -   xi) O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium        tetrafluoroborate (TBTU); and    -   xii) 4,5-Dicyanoimidazole.

This step may optionally be conducted in the presence of a solvent,non-limiting examples of said solvents include solvents chosen fromdimethylformamide, dimethylacetamide, tetrahydrofuran,methylenechloride, chloroform, 1,2-dichloroethane,1,1,1-trichloroethane, 1,2-dimethoxyethane, tert-butyl methyl ether,2-methyltetrahydrofuran, diethylene glycol dimethyl ether, dioxane, anddimethylsulfoxide. In another iteration, water can be used as aco-solvent for this reaction under certain known to the artisanconditions.

Step (b) Formation of a di-amine having the formula:

Step (b) relates to reacting the chiral di-amide formed in step (a) witha reducing agent to form a chiral diamine. Non-limiting examples ofreducing agents suitable for use in step (b) include chosen fromBH₃:DMS, BH₃:THF, B₂H₆, AlH₃, AlCl₃—LiAlH₄, NaBH₄-organic acidcomplexes, NaBH₄—BF₃Et₂O, and sodium bis(2-methoxyethoxy)-aluminumhydride.

This step may optionally be conducted in the presence of a solvent,non-limiting examples of said solvents include solvents chosen fromtetrahydrofuran, diethyl ether, and tert-butyl methyl ether.

Step (c) Formation of a chiral 2-imidazolidinone having the formula:

Step (c) relates to reacting the di-amine formed in step (b) with areagent which is capable of introducing a carbonyl group. Non-limitingexamples of reagents which are capable of introducing a carbonyl groupand thereby resulting in the cyclization of the compound formed in step(b) into a 2-imidazolidinone are reagents chosen from1,1′-carbonyldiimidazole, phosgene, triphosgene, dimethylpyrocarbonate,and di-tert-butyl-pyrocarbonate.

This step may optionally be conducted in the presence of a solvent,non-limiting examples of said solvents include solvents chosen fromacetonitrile, dimethylformamide, dimethylacetamide, tetrahydrofuran,methylenechloride, chloroform, 1,2-dichloroethane,1,1,1-trichloroethane, 1,2-dimethoxyethane, tert-butyl methyl ether,2-methyltetrahydro-furan, diethylene glycol dimethyl ether, dioxane, anddimethylsulfoxide.

Step (d) Formation of a 1-N-amino-2-imdazolidinone intermediate havingthe formula:

Step (d) relates to reacting the 2-imidazolidinone formed in step (c)under conditions wherein an amino group is formed at the 1-position ofthe 2-imidazolidinone ring.

A first iteration of this step relates to the introduction of an aminounit by way of a two step process, the first step (d)(i) encompasses thereaction of the chiral 2-imizolidinone with sodium nitrite in thepresence of an organic acid, for example, glacial acetic acid. Thereaction intermediate thus formed in step (d)(i) is then reduced in asecond step (d)(ii). A non-limiting example of a reducing reagentsuitable for use includes zinc metal. In this iteration, the organicacid in step (d)(i) can serve as a suitable solvent for both steps.

The chiral 1-N-amino-2-imidazolidinone in one iteration is present ingreater than 99% enantiomeric excess and is suitable for use directly inpreparation of the Kv 1.5 potassium channel blockers of the presentinvention.

The following is a specific example of the preparation of a compoundaccording to the present invention having enhanced enantiomeric purity.The skilled practitioner will know how to substitute the appropriatereagents, starting materials and purification methods known to thoseskilled in the art, in order to prepare additional compounds of thepresent invention having enhanced enantiomeric purity.

EXAMPLE 11 Compound 105:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone

Preparation of2-(R)-(4-methoxyphenyl)-2-[2-(4-methoxyphenyl)acetylamino]-acetamide: Asolution of (R)-2-amino-2-(4-methoxyphenyl)acetamide (200 g, 1.11 mol),triethylamine (124 g, 1.22 mol) in dimethylformamide (2 L) is cooled to5° C. in an ice bath and (4-methoxyphenyl)acetyl chloride (225 g, 187mL, 1.22 mol) is added dropwise at a rate which maintains thetemperature in a range from 5° C. to 7° C. After 1.5 hours theadditional stirring in the cold, the reaction solution is transferred toa vessel containing water (12 L). The solid which forms upon standing iscollected and rinsed several times with water. The material collected isdried to a constant weight affording 323.9 g (89% yield) of the desiredproduct. Analysis by chiral HPLC indicates 98.6% enantiomeric purity.

Preparation of1-(R)-(4-methoxyphenyl)-N¹-[2-(4-methoxyphenyl)ethyl]ethane-1,2-diamine:A solution of2-(R)-(4-methoxyphenyl)-2-[2-(4-methoxyphenyl)-acetylamino]-acetamide(316 g, 0.96 mol) in THF (2 L) is heated to 35° C. and borane dimethylsulfide (428 mL, 4.28 mol) is added over approximately 1 hour afterwhich the reaction is heated to reflux for 18 hours. After cooling thereaction solution to 8° C. sufficient 3N HCl (approx. 400 mL) is addeduntil the pH of the solution is approximately 1. The reaction solutionis then heated to reflux for 1 hour. The reaction is then cooled and thepH adjusted to 8 by the slow addition of 25% aqueous NaOH (300 mL). Theentire reaction solution is poured into a vessel containing a mixture ofCH₂Cl₂ (3 L) and water (1.5 L). The organic layer is decanted and thewater layer treated with CH₂Cl₂ (1.5 L). The organic layers arecombined, washed with brine (2.5 L) then dried over Na₂SO₄. The solventin removed in vacuo to afford 302 g (quantitative yield) of the desiredproduct as an amber colored oil.

Preparation of5-(R)-(4-methoxyphenyl)-1-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone:A solution of1-(R)-(4-methoxyphenyl)-N¹-[2-(4-methoxyphenyl)ethyl]ethane-1,2-diamine(446 g, 1.48 mol) in ethyl acetate (2.25 L) is placed in a water bathand 1,1′-carbonyldiimidazole (264 g, 1.62 mol) is added in portions. Thereaction is then heated to reflux for 1.5 hours after which the solutionis cooled, treated with 1N HCl (2×1.5 L), brine (2×1.5 L), dried overNa₂SO₄ and set aside in the cold. After standing the precipitate whichforms is removed by filtration and the solvent removed under reducedpressure to afford 468 g (96% yield) of the desired product. Chiral HPLCof the product thus obtained to have 99.5% of the desired (R) enantiomerpresent.

Preparation of1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone:A solution of5-(R)-(4-methoxyphenyl)-1-[2-(4-methoxy-phenyl)ethyl]-2-imidazolidinone(257 g, 0.79 mol) in glacial acetic acid (2.2 L) is cooled to 13° C. Asolution of sodium nitrite (76 g, 1.1 mol) in water (380 mL) is addeddropwise and the reaction is stirred an additional 1.5 hours. Thesolution is then cooled to 5° C. and Zn dust (194 g, 297 g-atm) is addedin portions over about 90 minutes. The resulting suspension is thenpoured into water (2 L) and CH₂Cl₂ (2 L) is added. The reaction mixtureis then cooled in an ice bath and treated with concentrated NH₄OH (2480mL). The solution is agitated and the organic phase decanted. Theaqueous layer is treated with an additional amount of CH₂Cl₂ (2 L), theorganic washings are combined, washed with brine, dried over Na₂SO₄, andthe solvent removed under reduced pressure to a crude product. ¹H NMR(300 MHz, CDCl₃) δ 7.14 (d, J=8.81, 2H, ArH), 7.00 (d, J=8.81, 2H, ArH),6.88 (d, J=8.51, 2H, ArH), 6.79 (d, J=8.51, 2H, ArH), 4.24 (m, 1H), 3.81(s, 3H, CH₃), 3.77 (s, 3H, CH₃), 3.51-3.72 (m, 2H), 3.13 (m, 1H),2.51-2.95 (m, 3H), 1.48-1.80 (br s, 2H).

The following is a non-limiting example of a chiral1-N-amino-2-imidazolidinone formed by the process of the presentinvention.

EXAMPLE 12 Compound 106:1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone

Preparation of1-(methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone:A solution of1-amino-3-[2-(4-methoxyphenyl)-ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone(247 g, 0.72 mol) in dichloromethane (2.35 L) and pyridine (174 mL, 2.15mol) is cooled in an ice bath to 18° C. Methanesulfonyl chloride (73 mL,0.94 mol) is added dropwise. The reaction is stirred cold for 2.5 hoursthen washed with 0.5 N HCl (2×1.5 L), brine (2×1.5 L) and dried(Na₂SO₄). The solvent is then removed in vacuo to afford a mixture ofthe desired product (75%) and unreacted starting material (25%) which isseparated by liquid chromatography. [α]²⁰ _(D) −39.83 (c 0.89, CHCl₃) ¹HNMR (300 MHz, CDCl₃) δ 7.16 (d, J=8.81, 2H, ArH), 7.02 (d, J=8.51, 2H,ArH), 6.91 (d, J=8.81, 2H, ArH), 6.80 (d, J=8.81, 2H, ArH), 4.41 (m,1H), 3.92 (m, 1H), 3.82 (s, 3H, CH₃), 3.77 (s, 3H, CH₃), 3.60-3.72 (m,1H), 3.30 (m, 1H), 3.03 (s, 3H, CH₃), 2.87-2.98 (m, 1H), 2.53-2.79 (m,3H). MS 418 (MH⁺). Anal. Calcd. for C₂₁H₂₇N₃O₄S¼H₂O: C, 59.77, H, 6.57;N, 9.96. Found: C, 59.82, H, 6.06; N, 9.85. FAB-HRMS: anal. calcd forC₂₁H₂₇N₃O₄S: 418.18005. Found: 418.17960.

Further compounds according to the present invention include:

Compound 107:N-{(4S)-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₀H₂₅N₃O₅S+H+, 420.15877; found (ESI, [M+H]+Obs'd),420.1592; HPLC Retention time, 2.8 min.

Compound 108: tert-butyl{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}(quinolin-3-ylmethyl)carbamate;HRMS: calcd for C₃₅H₄₀N₄O₄+H+, 581.31223; found (ESI, [M+H]+Obs'd),581.3127; HPLC Retention time, 3.4 min.

Compound 109: tert-butyl[2-({4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}amino)-2-oxoethyl]methylcarbamate;CHN anaylsis: C, 71.75; H, 6.83; N, 9.38, Calculated C₃₅H₄₀N₄O₄+0.25H₂O,C, 71.83; H, 6.98, N, 9.57; HPLC Retention time, 5.95 min.

Compound 110:1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(trifluoromethoxy)phenyl]imidazolidin-2-one;HRMS: calcd for C₁₉H₂₀F₃N₃O₃+H+, 396.15295; found (ESI, [M+H]⁺),396.1535; HPLC Retention time, 2.9 min.

Compound 111:N-{4,4-diethyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₁₇H₂₇N₃O₄S+H+, 370.17950; found (ESI, [M+H]+Obs'd),370.1799; HPLC Retention time, 2.8 min.

Compound 112:4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-piperazin-1-ylimidazolidin-2-one;HRMS: calcd for C₂₆H₃₆N₄O₂+H+, 437.29110; found (ESI, [M+H]+Obs'd),437.2917; HPLC Retention time, 3.0 min.

Compound 113:N-{3-[2-(4-ethoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₁H₂₇N₃O₅S+H+, 434.17442; found (ESI, [M+H]+Obs'd),434.1746; HPLC Retention time, 2.9 min.

Compound 114:N-{4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-(methylsulfonyl)ethanesulfonamide;HRMS: calcd for C₂₄H₃₁N₃O₆S₂+H+, 522.17270; found (ESI, [M+H]+Obs'd),522.1730; HPLC Retention time, 3.0 min.

Compound 115:2-({4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamoyl)acetamide;HRMS: calcd for C₂₁H₂₆N₄O₆S+H+, 463.16458; found (ESI, [M+H]+Obs'd),463.1651; HPLC Retention time, 2.7 min.

Compound 116: tert-butyl({4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamoyl)carbamate;HRMS: calcd for C₂₅H₃₄N₄O₆S+H+, 519.22718; found (ESI, [M+H]+Obs'd),519.2282; HPLC Retention time, 2.9 min.

Compound 117:4-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N-methylpiperazine-1-carboxamide;HRMS: calcd for C₂₈H₃₉N₅O₃+H+, 494.31257; found (ESI, [M+H]+Obs'd),494.3130; HPLC Retention time, 3.0 min.

Compound 118:N-[4-(4-tert-butylphenyl)-3-(2-{4-[2-(dimethylamino)ethoxy]phenyl}ethyl)-2-oxoimidazolidin-1-yl]methanesulfonamide;HRMS: calcd for C₂₆H₃₈N₄O₄S+H+, 503.26865; found (ESI, [M+H]+ Calc'd),503.2686; HPLC Retention time, 2.9 min.

Compound 119:1-amino-4-(4-tert-butylphenyl)-3-[3-(4-methoxyphenyl)propyl]imidazolidin-2-one;HRMS: calcd for C₂₃H₃₁N₃O₂+H+, 382.24890; found (ESI, [M+H]+Obs'd),382.2495; HPLC Retention time, 3.1 min.

Compound 120:N-{4-(4-fluorobenzyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₀H₂₄FN₃O₄S+H+, 422.15443; found (ESI, [M+H]+Obs'd),422.1551; HPLC Retention time, 2.9 min.

Compound 121:4-(4-tert-butylphenyl)-1-{[2-(1H-imidazol-1-yl)ethyl]amino}-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₂₇H₃₅N₅O₂+H+, 462.28635; found (ESI, [M+H]+Obs'd),462.2868; HPLC Retention time, 3.1 min.

Compound 122:N-{4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-pyridin-3-ylacetamide;HRMS: calcd for C₂₈H₃₀N₄O₃+H+, 471.23907; found (ESI, [M+H]+Obs'd),471.2397; HPLC Retention time, 2.9 min.

Compound 123:4-(4-tert-butylphenyl)-1-{[4-(diethylamino)benzyl]amino}-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₃₃H₄₄N₄O₂+H+, 529.35370; found (ESI, [M+H]+Obs'd),529.3545; HPLC Retention time, 3.6 min.

Compound 1244-(4-cyclopropylphenyl)-1-(1,1-dioxidoisothiazolidin-2-yl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₂₄H₂₉N₃O₄S+H+, 456.19515; found (ESI, [M+H]+Obs'd),456.1958; HPLC Retention time, 3.0 min.

Compound 125:N-{4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-morpholin-4-ylethanesulfonamide;HRMS: calcd for C₂₆H₃₄N₄O₇S+H+, 547.22210; found (ESI, [M+H]+Obs'd),547.2225; HPLC Retention time, 2.7 min.

Compound 126:N-{4-(4-methoxyphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-oxoimidazolidin-1-yl}-1-(methylsulfonyl)methanesulfonamide;HRMS: calcd for C₂₂H₂₉N₃O₇S₂+H+, 512.15197; found (ESI, [M+H]+Obs'd),512.1520; HPLC Retention time, 2.8 min.

Compound 127:N-{4-(4-cyclopropylphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-oxoimidazolidin-1-yl}-1-(methylsulfonyl)methanesulfonamide;HRMS: calcd for C₂₄H₃₁N₃O₆S₂+H+, 522.17270; found (ESI, [M+H]+Obs'd),522.1728; HPLC Retention time, 3.0 min.

Compound 128:N-{4-butyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₁₇H₂₇N₃O₄S+H+, 370.17950; found (ESI, [M+H]+Obs'd),370.1799; HPLC Retention time, 2.9 min.

Compound 129:1-amino-4-(4-fluorobenzyl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₁₉H₂₂FN₃O₂+H+, 344.17688; found (ESI, [M+H]+Obs'd),344.1774; HPLC Retention time, 2.8 min.

Compound 130:4-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N,N-dimethylpiperazine-1-carboxamide;HRMS: calcd for C₂₉H₄₁N₅O₃+H+, 508.32822; found (ESI, [M+H]+Obs'd),508.3286; HPLC Retention time, 3.1 min.

Compound 131:1-amino-4-(4-methoxyphenyl)-3-(3-phenylpropyl)imidazolidin-2-one. Analternative name for this compound is1-Amino-3-(3-phenylpropyl)-4-(4-methoxyphenyl)-2-imidazolidinone; HRMS:calcd for C₁₉H₂₃N₃O₂+H+, 326.18630; found (ESI, [M+H]+Obs'd), 326.1863;HPLC Retention time, 2.8 min.

Compound 132:2-(N-(4-(4-cyclopropylphenyl)-3-(4-methoxyphenethyl)-2-oxoimidazolidin-1-yl)sulfamoyl)-N-(2-(dimethylamino)-2-oxoethyl)-N-methylacetamide;HRMS: calcd for C₂₈H₃₇N₅O₆S+H+, 572.25373; found (ESI, [M+H]+Obs'd),572.2541; HPLC Retention time, 2.9 min.

Compound 133:N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N-(phenylsulfonyl)benzenesulfonamide;HRMS: calcd for C₃₂H₃₃N₃O₆S₂+H+, 620.18835; found (ESI, [M+H]+Obs'd),620.1885; HPLC Retention time, 3.5 min.

Compound 134:N-{3-[2-(4-methoxyphenyl)ethyl]-2-oxo-4-(1-phenylcyclopropyl)imidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;HRMS: calcd for C₂₇H₃₀N₄O₄S+H+, 507.20605; found (ESI, [M+H]+Obs'd),507.2064; HPLC Retention time, 2.9 min.

Compound 135: methyl3-amino-4-({4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}amino)benzoate;HRMS: calcd for C₂₈H₃₂N₄O₄+H+, 489.24963; found (ESI, [M+H]⁺), 489.2495;HPLC Retention time, 3.1 min.

Compound 136:N-(cyclopropylmethyl)-2-({(4R)-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamoyl)acetamide;HRMS: calcd for C₂₅H₃₂N₄O₆S+H+, 517.21153; found (ESI, [M+H]+Obs'd),517.2118; HPLC Retention time, 2.9 min.

Compound 137:N-{4-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₁₉H₂₂FN₃O₄S+H+, 408.13878; found (ESI, [M+H]+Obs'd),408.1394; HPLC Retention time, 2.8 min.

Compound 138:4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-{[(1-methyl-1H-imidazol-2-yl)methyl]amino}imidazolidin-2-one;HRMS: calcd for C₂₅H₃₁N₅O₂+H+, 434.25505; found (ESI, [M+H]+Obs'd),434.2550; HPLC Retention time, 2.9 min.

Compound 139:N-{4-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;HRMS: calcd for C₂₄H₂₅FN₄O₄S+H+, 485.16533; found (ESI, [M+H]+Obs'd),485.1660; HPLC Retention time, 2.9 min.

Compound 140:N-{3-[2-(4-methoxyphenyl)ethyl]-2-oxo-4-(1-phenylcyclopropyl)imidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₂H₂₇N₃O₄S+H+, 430.17950; found (ESI, [M+H]+Obs'd),430.1801; HPLC Retention time, 2.9 min.

Compound 141:1-amino-4-[4-(2-methoxyethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₂₁H₂₇N₃O₄+H+, 386.20743; found (ESI, [M+H]+Obs'd),386.2077; HPLC Retention time, 2.6 min.

Compound 142:N-[3-{2-[4-(difluoromethoxy)phenyl]ethyl}-4-(4-methoxyphenyl)-2-oxoimidazolidin-1-yl]methanesulfonamide;HRMS: calcd for C₂₀H₂₃F₂N₃O₅S+H+, 456.13992; found (ESI, [M+H]+Obs'd),456.1402; HPLC Retention time, 2.9 min.

Compound 143:N-{3-[2-(4-methoxyphenyl)ethyl]-2-oxo-4-quinolin-6-ylimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₂H₂₄N₄O₄S+H+, 441.15910; found (ESI, [M+H]+Obs'd),441.1595; HPLC Retention time, 2.6 min.

Compound 144:N-{4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[2-(3,4-dimethoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₂H₂₇N₃O₇S+H+, 478.16425; found (ESI, [M+H]+Obs'd),478.1648; HPLC Retention time, 2.6 min.

Compound 145:N-{4-cyclohexyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₁₉H₂₉N₃O₄S+H+, 396.19515; found (ESI, [M+H]+Obs'd),396.1959; HPLC Retention time, 3.0 min.

Compound 146: tert-butyl{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}[2-(1H-imidazol-1-yl)ethyl]carbamate;HRMS: calcd for C₃₂H₄₃N₅O₄+H+, 562.33878; found (ESI, [M+H]+Obs'd),562.3392; HPLC Retention time, 3.3 min.

Compound 147:N-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}pyrazine-2-carboxamide;HRMS: calcd for C₂₇H₃₁N₅O₃+H+, 474.24997; found (ESI, [M+H]+Obs'd),474.2505; HPLC Retention time, 3.1 min.

Compound 148:N-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1,1,1-trifluoromethanesulfonamide;HRMS: calcd for C₂₃H₂₈F₃N₃O₄S+H+, 500.18254; found (ESI, [M+H]+Obs'd),500.1827; HPLC Retention time, 2.9 min.

Compound 149:N-{3-[2-(4-methoxyphenyl)ethyl]-4-(6-methoxypyridin-3-yl)-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₁₉H₂₄N₄O₅S+H+, 421.15402; found (ESI, [M+H]+Obs'd),421.1547; HPLC Retention time, 2.6 min.

Compound 150:4-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}piperazine-1-carboxamide;HRMS: calcd for C₂₇H₃₇N₅O₃+H+, 480.29692; found (ESI, [M+H]+Obs'd),480.2971; HPLC Retention time, 3.0 min.

Compound 151:N-{4-[4-(2-methoxyethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₂H₂₉N₃O₆S+H+, 464.18498; found (ESI, [M+H]+Obs'd),464.1854; HPLC Retention time, 2.8 min.

Compound 152:N-[4-(4-methoxyphenyl)-2-oxo-3-{2-[4-(trifluoromethoxy)phenyl]ethyl}imidazolidin-1-yl]methanesulfonamide;HRMS: calcd for C₂₀H₂₂F₃N₃O₅S+H+, 474.13050; found (ESI, [M+H]+Obs'd),474.1309; HPLC Retention time, 3.1 min.

Compound 153:N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-(methylsulfonyl)methanesulfonamide;HRMS: calcd for C₂₁H₂₇N₃O₇S₂+H+, 498.13632; found (ESI, [M+H]+Obs'd),498.1366; HPLC Retention time, 2.8 min.

Compound 154:1-amino-3-{2-[4-(difluoromethoxy)phenyl]ethyl}-4-(4-methoxyphenyl)imidazolidin-2-one;HRMS: calcd for C₁₉H₂₁F₂N₃O₃+H+, 378.16237; found (ESI, [M+H]+Obs'd),378.1627; HPLC Retention time, 2.8 min.

Compound 155:1-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-3-phenylurea;HRMS: calcd for C₂₇H₃₀N₄O₃+H+, 459.23907; found (ESI, [M+H]⁺), 459.2393;HPLC Retention time, 3.1 min.

Compound 156:1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(1-phenylcyclopropyl)imidazolidin-2-one;HRMS: calcd for C₂₁H₂₅N₃O₂+H+, 352.20195; found (ESI, [M+H]+Obs'd),352.2025; HPLC Retention time, 2.8 min.

Compound 157:N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N-[(1-methyl-1H-imidazol-2-yl)methyl]methanesulfonamide;HRMS: calcd for C₂₆H₃₃N₅O₄S+H+, 512.23260; found (ESI, [M+H]+Obs'd),512.2333; HPLC Retention time, 3.0 min.

Compound 158:N-{4-(3,4-dimethoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₁H₂₇N₃O₆S+H+, 450.16933; found (ESI, [M+H]+Obs'd),450.1695; HPLC Retention time, 2.7 min.

Compound 159:1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)imidazolidin-2-one.An alternative name for this compound is1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)-2-imidazolidinone;HRMS: calcd for C₁₉H₂₃N₃O₂+H+, 326.18630; found (ESI, [M+H]+Obs'd),326.1866; HPLC Retention time, 2.8 min.

Compound 160:N-{4-butyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;HRMS: calcd for C₂₂H₃₀N₄O₄S+H+, 447.20605; found (ESI, [M+H]+Obs'd),447.2066; HPLC Retention time, 2.9 min.

Compound 161:4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-{[(1-oxidopyridin-4-yl)methyl]amino}imidazolidin-2-one;HRMS: calcd for C₂₆H₃₀N₄O₃+H+, 447.23907; found (ESI, [M+H]⁺), 447.2398;HPLC Retention time, 2.7 min.

Compound 162:N-{4,4-diethyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;HRMS: calcd for C₂₂H₃₀N₄O₄S+H+, 447.20605; found (ESI, [M+H]+Obs'd),447.2065; HPLC Retention time, 2.8 min.

Compound 163:1-amino-4-[1-(4-fluorophenyl)cyclopropyl]-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₂₁H₂₄FN₃O₂+H+, 370.19253; found (ESI, [M+H]+Obs'd),370.1929; HPLC Retention time, 2.8 min.

Compound 164:1-amino-4-(4-isopropoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;HRMS: calcd for C₂₁H₂₇N₃O₃+H+, 370.21252; found (ESI, [M+H]+Obs'd),370.2131; HPLC Retention time, 2.9 min.

Compound 165:N-{4-[1-(4-fluorophenyl)cyclopropyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;HRMS: calcd for C₂₂H₂₆FN₃O₄S+H+, 448.17008; found (ESI, [M+H]+Obs'd),448.1707; HPLC Retention time, 2.9 min.

Compound 166:N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-4-methylpiperazine-1-sulfonamide;HRMS: calcd for C₂₅H₃₅N₅O₄S+H+, 502.24825; found (ESI, [M+H]+Obs'd),502.2489; HPLC Retention time, 8.6 min.

Compound 167:N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamide;HRMS: calcd for C₁₉H₂₄N₄O₅S+H+, 421.15402; found (ESI, [M+H]+Obs'd),421.1539; HPLC Retention time, 2.7 min.

Compound 168:2-(4-acetylpiperazin-1-yl)-N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-oxoethanesulfonamide;HRMS: calcd for C₂₇H₃₅N₅O₇S+H+, 574.23300; found (ESI, [M+H]+Obs'd),574.2327; HPLC Retention time, 2.7 min.

Compound 169:N-[4-(4-tert-butylphenyl)-3-{2-[4-(2-morpholin-4-ylethoxy)phenyl]ethyl}-2-oxoimidazolidin-1-yl]methanesulfonamide;HRMS: calcd for C₂₈H₄₀N₄O₅S+H+, 545.27922; found (ESI, [M+H]+Obs'd),545.2797; HPLC Retention time, 3.0 min.

Compound 170:N-{(4R)-4-[4-(difluoromethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide:MS 456 (MH⁺); HPLC Retention time, 9.2 minutes with an Xterra RP18, 3.5u, 150×4.6 mm column with a gradient of 85/15-5/95 (Ammon. Form. Buff.Ph=3.5/ACN+MeOH) for 10 min, hold 4 min.

Compound 171:N-{(4S)-4-[4-(difluoromethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide.MS 456 (MH⁺); HPLC Retention time, 9.2 minutes with an Xterra RP18, 3.5u, 150×4.6 mm column with a gradient of 85/15-5/95 (Ammon. Form. Buff.Ph=3.5/ACN+MeOH) for 10 min, hold 4 min.

Compound 172:N-{(4R)-4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;MS 446 (M+H), HPLC Retention time: 10.5 minutes in an HPLC with anXterra RP18, 3.5 u, 150×4.6 mm column with a gradient of 85/15-5/95(Ammon. Form. Buff. Ph=3.5/ACN+MeOH) for 10 min, hold 4 min.

Compound 173:N-{(4S)-4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;MS 446 (M+H), HPLC Retention time: 10.5 minutes in an HPLC with anXterra RP18, 3.5 u, 150×4.6 mm column with a gradient of 85/15-5/95(Ammon. Form. Buff. Ph=3.5/ACN+MeOH) for 10 min, hold 4 min.

Compound 174:[[[4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl]amino]sulfonyl]aceticacid. ¹H NMR (CDCl₃) δ 8.03 (bs, 1H), 7.19 (d, J=8.4 Hz, 2H), 7.11 (d,J=8.1 Hz, 2H), 7.05 (m, 2H), 6.84 (m, 2H), 4.51 (t, J=8.4 Hz, 1H), 4.30(s, 2H), 4.01 (t, J=8.7, 1H), 3.81 (s, 3H), 3.66 (m, 1H), 3.51 (m, 1H),2.95 (m, 1H), 2.64 (m, 1H), 1.93 (m, 1H), 1.02 (m, 2H), 0.74 (m, 2H). MS652 (MH⁺). Anal. calcd. for C₂₃H₂₇N₃O₆S¼C₄H₁₀O: C, 58.58; H, 6.04; N,8.54. Found: C, 58.37; H, 6.01; N, 8.35

Compound 175:1-amino-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one:¹H-NMR (DMSO-d₆): ? 7.50 (d, J=8.1 Hz, 2H), 7.33 (d, J=8.1 Hz, 2H), 7.14(d, J=8.2 Hz, 2H), 7.04 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.2 Hz, 2H), 6.82(d, J=8.4 Hz, 2H), 4.68 (t, J=7.8 Hz, 1H), 3.84 (t, J=7.8 Hz, 1H), 3.79(s, 3H), 3.71 (s, 3H), 3.55 (m, 1H), 3.24 (t, J=8.1 Hz, 1H), 2.64 (m,3H), 2.52 (m, 2H), 2.30 (s, 3H). MS m/z (ESI, positive): 342 [M+H]⁺.This compound was isolated as the p-toluene sulfonic acid salt.

Compound 176:1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone

Compound 177:1-({[(2,2-Dimethyl-2-hydroxy-1-methylethyl)amino]-2-oxoethyl}sulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 178:1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-cyclopropylphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone:

Compound 179:N-{4-(Cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-2-dimethylsulfamoyl-acetamide

Compound 180:1-[(2-Amino-2-oxoethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)propyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 181:1-[(N-Methyl-N-methylsulfonyl)amino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Compound 182:1-[(N-Methyl-N-phenylsulfonyl)amino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone

Compound 183:(S)-1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone

Compound 184:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(3,4-dimethylphenyl)-2-imidazolidinone

Compound 185:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone

Compound 186:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-tert-butylphenyl)-2-imidazolidinone:MS: 46 (M+H) HPLC Retention time: 10.5 minutes in an HPLC with an XterraRP18, 3.5 u, 150×4.6 mm column with a gradient of 85/15-5/95 (Ammon.Form. Buff. Ph=3.5/ACN+MeOH) for 10 min, hold 4 min

Compound 187:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 188:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(3,4-dimethylphenyl)-2-imidazolidinone

Compound 189:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(4-methoxyphenyl)-2-imidazolidinone

Compound 190:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(4-tert-butylphenyl)-2-imidazolidinone

Compound 191:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 192:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(3,4-dimethylphenyl)-2-imidazolidinone

Compound 193:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(4-methoxyphenyl)-2-imidazolidinone

Compound 194:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(4-tert-butylphenyl)-2-imidazolidinone.MS: 46 (M+H) HPLC Retention time: 10.5 minutes in an HPLC with an XterraRP18, 3.5 u, 150×4.6 mm column with a gradient of 85/15-5/95 (Ammon.Form. Buff. Ph=3.5/ACN+MeOH) for 10 min, hold 4 min

Compound 195:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 196:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(3,4-dimethylphenyl)-2-imidazolidinone

Compound 197:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(4-methoxyphenyl)-2-imidazolidinone

Compound 198:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(4-tert-butylphenyl)-2-imidazolidinone

Compound 199:1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 200:(R)-1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone

Compound 201:1-{[2-(cyclopropylamino)-2-oxoethyl]sulfonylamino}-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone.¹H NMR (CDCl₃) δ 8.43 (d, J=3.6 Hz, 1H), 7.12 (m, 5H), 7.06 (m, 2H),6.83 (m, 2H), 4.49 (t, J=8.4 Hz, 1H), 4.00 (m, 3H), 3.80 (s, 3H), 3.68(m, 1H), 3.42 (m, 1H), 3.42 (m, 1H), 2.95 (m, 1H), 2.86 (m, 1H), 2.72(m, 1H), 2.65 (m, 1H), 1.93 (m, 1H), 1.01 (m, 2H), 0.83 (m, 2H), 0.74(m, 2H), 0.64 (m, 2H). MS 513 (MH⁺). Anal. calcd. for C₂₆H₃₂N₄O₅S½H₂O:C, 59.87; H, 6.38; N, 10.74. Found: C, 59.62; H, 6.14; N, 10.49.

Compound 202:1-[[(Dimethylamino)sulfonyl]acetylamino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone

Compound 203:1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-cyclo-propylphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone

HPLC Conditions for compounds 109-169 were as follows: Column: BDSHypersil C8; mobile phase A: 10 mM NH₄OAC in 95% water/5% ACN (pipette6.67 mL of 7.5 M NH₄OAC solution into 4743 mL H₂O, then add 250 mL ofACN to the solution and mix.); mobile phase B: 10 mM NH₄OAC in 5%water/95% ACN (pipette 6.67 mL of 7.5 M NH₄OAC solution into 243 mL H₂O.Then add 4750 mL of ACN to the solution and mix.); flow Rate: 0.800mL/min; column Temperature: 40° C.; injection Volume: 5

L; UV: monitor 214 nm and 254 nm; gradient table (time (min)/% B):0.0/0; 2.5/100; 4.0/100; 4.1/0; 5.5/0.

Compounds listed and described herein have been found in many instancesto exhibit activities (e.g., IC₅₀ in the assays described-or referencedherein) at a concentration below 1 micromolar (μM). For certain of thecompounds of the present invention, activity levels at 1.0 μM wereundetectable in the Kv1.5 Patch Clamp EP assay described herein.Although these compounds were not tested at higher concentrations, it isbelieved that they would demonstrate measurable activity at higherconcentrations.

Compounds of the present invention are effective as Kv1.5 potassiumchannel inhibitors. Accordingly, compounds of the present invention canbe used to prevent or treat conditions that can be affected byinhibition of Kv1.5 potassium channel.

Compounds of the present invention can be used to treat or preventcardiac arrhythmias, including atrial fibrillation and flutter. Inpreferred embodiments, compounds of the present invention are capable ofinhibiting Kv1.5 potassium channels while having little or no inhibitoryeffect on other ion channels in heart, including for example, ionchannels in the ventricles. Accordingly, in preferred embodiments,compounds of the present invention will prevent or treat cardiacarrhythmia while avoiding some of the common complications typicallyassociated with inhibition of ion channels in the heart, including, forexample, a prolongation of the QT interval and an increased propensityfor life threatening ventricular arrhythmias.

Compounds of the present invention can be used to treat or preventatrial arrhythmias, including atrial fibrillation and atrial flutter, aswell as conditions associated with atrial arrhythmias, including, forexample, thromboembolism, stroke, and heart failure.

Compounds of the present invention can be used to produce long-term, aswell as short term maintenance periods free of arrhythmia in patientswith persistent or chronic atrial arrhythmias.

Compounds of the present invention can also be used to prophylacticlytreat post surgical atrial arrhthmias.

Methods of the present invention thus include methods of inhibitingKv1.5 potassium channel; methods of inhibiting Kv1.5 potassium channelswhile having little or no inhibitory effect on other ion channels inheart, including for example, ion channels in the ventricles; methods oftreating or preventing cardiac arrhythmias, including atrialfibrillation and flutter; methods for treating or preventing conditionsassociated with atrial arrhythmias, including, for example,thromboembolism, stroke, and heart failure; methods for producinglong-term, as well as short term maintenance periods free of arrhythmiain patients with persistent or chronic atrial arrhythmias; and methodsfor prophylacticly treating post surgical atrial arrhthmias. The methodscan comprise administering an effective amount of a compound orcomposition of the present invention to a subject.

The present invention also relates to the use of the compounds accordingto the present invention in the manufacture of a medicament for thetreatment or prevention of atrial arrhythmias and related disorders.

Formulations

The present invention also relates to compositions or formulations whichcomprise the Kv1.5 potassium channel inhibitors according to the presentinvention. In general, the compositions of the present inventioncomprise an effective amount of one or more 1-N-amino-2-imidazolidinonesand salts thereof according to the present invention which are effectivefor providing atrial-selective antiarrhythmia and one or moreexcipients.

For the purposes of the present invention the term “excipient” and“carrier” are used interchangeably throughout the description of thepresent invention and said terms are defined herein as, “ingredientswhich are used in the practice of formulating a safe and effectivepharmaceutical composition.”

The formulator will understand that excipients are used primarily toserve in delivering a safe, stable, and functional pharmaceutical,serving not only as part of the overall vehicle for delivery but also asa means for achieving effective absorption by the recipient of theactive ingredient. An excipient may fill a role as simple and direct asbeing an inert filler, or an excipient as used herein may be part of apH stabilizing system or coating to insure delivery of the ingredientssafely to the stomach. The formulator can also take advantage of thefact the compounds of the present invention have improved cellularpotency, pharmacokinetic properties, as well as improved oralbioavailability.

The present teachings also provide pharmaceutical compositions thatinclude at least one compound described herein and one or morepharmaceutically acceptable carriers, excipients, or diluents. Examplesof such carriers are well known to those skilled in the art and can beprepared in accordance with acceptable pharmaceutical procedures, suchas, for example, those described in Remington's Pharmaceutical Sciences,17th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton,Pa. (1985), the entire disclosure of which is incorporated by referenceherein for all purposes. As used herein, “pharmaceutically acceptable”refers to a substance that is acceptable for use in pharmaceuticalapplications from a toxicological perspective and does not adverselyinteract with the active ingredient. Accordingly, pharmaceuticallyacceptable carriers are those that are compatible with the otheringredients in the formulation and are biologically acceptable.Supplementary active ingredients can also be incorporated into thepharmaceutical compositions.

Compounds of the present teachings can be administered orally orparenterally, neat or in combination with conventional pharmaceuticalcarriers. Applicable solid carriers can include one or more substanceswhich can also act as flavoring agents, lubricants, solubilizers,suspending agents, fillers, glidants, compression aids, binders ortablet-disintegrating agents, or encapsulating materials. The compoundscan be formulated in conventional manner, for example, in a mannersimilar to that used for known antiarrhythmic agents. Oral formulationscontaining a compound disclosed herein can comprise any conventionallyused oral form, including tablets, capsules, buccal forms, troches,lozenges and oral liquids, suspensions or solutions. In powders, thecarrier can be a finely divided solid, which is an admixture with afinely divided compound. In tablets, a compound disclosed herein can bemixed with a carrier having the necessary compression properties insuitable proportions and compacted in the shape and size desired. Thepowders and tablets can contain up to 99% of the compound.

Capsules can contain mixtures of one or more compound(s) disclosedherein with inert filler(s) and/or diluent(s) such as pharmaceuticallyacceptable starches (e.g., corn, potato or tapioca starch), sugars,artificial sweetening agents, powdered celluloses (e.g., crystalline andmicrocrystalline celluloses), flours, gelatins, gums, and the like.

Useful tablet formulations can be made by conventional compression, wetgranulation or dry granulation methods and utilize pharmaceuticallyacceptable diluents, binding agents, lubricants, disintegrants, surfacemodifying agents (including surfactants), suspending or stabilizingagents, including, but not limited to, magnesium stearate, stearic acid,sodium lauryl sulfate, talc, sugars, lactose, dextrin, starch, gelatin,cellulose, methyl cellulose, microcrystalline cellulose, sodiumcarboxymethyl cellulose, carboxymethylcellulose calcium,polyvinylpyrrolidine, alginic acid, acacia gum, xanthan gum, sodiumcitrate, complex silicates, calcium carbonate, glycine, sucrose,sorbitol, dicalcium phosphate, calcium sulfate, lactose, kaolin,mannitol, sodium chloride, low melting waxes, and ion exchange resins.Surface modifying agents include nonionic and anionic surface modifyingagents. Representative examples of surface modifying agents include, butare not limited to, poloxamer 188, benzalkonium chloride, calciumstearate, cetostearl alcohol, cetomacrogol emulsifying wax, sorbitanesters, colloidal silicon dioxide, phosphates, sodium dodecylsulfate,magnesium aluminum silicate, and triethanolamine. Oral formulationsherein can utilize standard delay or time-release formulations to alterthe absorption of the compound(s). The oral formulation can also consistof administering a compound disclosed herein in water or fruit juice,containing appropriate solubilizers or emulsifiers as needed.

Liquid carriers can be used in preparing solutions, suspensions,emulsions, syrups, elixirs, and for inhaled delivery. A compound of thepresent teachings can be dissolved or suspended in a pharmaceuticallyacceptable liquid carrier such as water, an organic solvent, or amixture of both, or pharmaceutically acceptable oils or fats. The liquidcarrier can contain other suitable pharmaceutical additives such assolubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoringagents, suspending agents, thickening agents, colors, viscosityregulators, stabilizers, and osmo-regulators. Examples of liquidcarriers for oral and parenteral administration include, but are notlimited to, water (particularly containing additives as describedherein, e.g., cellulose derivatives such as a sodium carboxymethylcellulose solution), alcohols (including monohydric alcohols andpolyhydric alcohols, e.g., glycols) and their derivatives, and oils(e.g., fractionated coconut oil and arachis oil). For parenteraladministration, the carrier can be an oily ester such as ethyl oleateand isopropyl myristate. Sterile liquid carriers are used in sterileliquid form compositions for parenteral administration. The liquidcarrier for pressurized compositions can be halogenated hydrocarbon orother pharmaceutically acceptable propellants.

Liquid pharmaceutical compositions, which are sterile solutions orsuspensions, can be utilized by, for example, intramuscular,intraperitoneal or subcutaneous injection. Sterile solutions can also beadministered intravenously. Compositions for oral administration can bein either liquid or solid form.

Preferably the pharmaceutical composition is in unit dosage form, forexample, as tablets, capsules, powders, solutions, suspensions,emulsions, granules, or suppositories. In such form, the pharmaceuticalcomposition can be sub-divided in unit dose(s) containing appropriatequantities of the compound. The unit dosage forms can be packagedcompositions, for example, packeted powders, vials, ampoules, prefilledsyringes or sachets containing liquids. Alternatively, the unit dosageform can be a capsule or tablet itself, or it can be the appropriatenumber of any such compositions in package form. Such unit dosage formcan contain from about 1 mg/kg of compound to about 500 mg/kg ofcompound, and can be given in a single dose or in two or more doses.Such doses can be administered in any manner useful in directing thecompound(s) to the recipient's bloodstream, including orally, viaimplants, parenterally (including intravenous, intraperitoneal andsubcutaneous injections), rectally, vaginally, and transdermally.

When administered for the treatment or inhibition of a particulardisease state or disorder, it is understood that an effective dosage canvary depending upon the particular compound utilized, the mode ofadministration, and severity of the condition being treated, as well asthe various physical factors related to the individual being treated. Intherapeutic applications, a compound of the present teachings can beprovided to a patient already suffering from a disease in an amountsufficient to cure or at least partially ameliorate the symptoms of thedisease and its complications. The dosage to be used in the treatment ofa specific individual typically must be subjectively determined by theattending physician. The variables involved include the specificcondition and its state as well as the size, age and response pattern ofthe patient.

In some cases, it may be desirable to administer a compound directly tothe airways of the patient, using devices such as, but not limited to,metered dose inhalers, breath-operated inhalers, multidose dry-powderinhalers, pumps, squeeze-actuated nebulized spray dispensers, aerosoldispensers, and aerosol nebulizers. For administration by intranasal orintrabronchial inhalation, the compounds of the present teachings can beformulated into a liquid composition, a solid composition, or an aerosolcomposition. The liquid composition can include, by way of illustration,one or more compounds of the present teachings dissolved, partiallydissolved, or suspended in one or more pharmaceutically acceptablesolvents and can be administered by, for example, a pump or asqueeze-actuated nebulized spray dispenser. The solvents can be, forexample, isotonic saline or bacteriostatic water. The solid compositioncan be, by way of illustration, a powder preparation including one ormore compounds of the present teachings intermixed with lactose or otherinert powders that are acceptable for intrabronchial use, and can beadministered by, for example, an aerosol dispenser or a device thatbreaks or punctures a capsule encasing the solid composition anddelivers the solid composition for inhalation. The aerosol compositioncan include, by way of illustration, one or more compounds of thepresent teachings, propellants, surfactants, and co-solvents, and can beadministered by, for example, a metered device. The propellants can be achlorofluorocarbon (CFC), a hydrofluoroalkane (HFA), or otherpropellants that are physiologically and environmentally acceptable.

Compounds described herein can be administered parenterally orintraperitoneally. Solutions or suspensions of these compounds can beprepared in water suitably mixed with a surfactant such ashydroxyl-propylcellulose. Dispersions can also be prepared in glycerol,liquid polyethylene glycols, and mixtures thereof in oils. Underordinary conditions of storage and use, these preparations typicallycontain a preservative to inhibit the growth of microorganisms.

The pharmaceutical forms suitable for injection can include sterileaqueous solutions or dispersions and sterile powders for theextemporaneous preparation of sterile injectable solutions ordispersions. In some embodiments, the form can sterile and its viscositypermits it to flow through a syringe. The form preferably is stableunder the conditions of manufacture and storage and can be preservedagainst the contaminating action of microorganisms such as bacteria andfungi. The carrier can be a solvent or dispersion medium containing, forexample, water, ethanol, polyol (e.g., glycerol, propylene glycol andliquid polyethylene glycol), suitable mixtures thereof, and vegetableoils.

Compounds described herein can be administered transdermally, i.e.,administered across the surface of the body and the inner linings ofbodily passages including epithelial and mucosal tissues. Suchadministration can be carried out using the compounds of the presentteachings including pharmaceutically acceptable salts, hydrates, oresters thereof, in lotions, creams, foams, patches, suspensions,solutions, and suppositories (rectal and vaginal).

Transdermal administration can be accomplished through the use of atransdermal patch containing a compound, such as a compound disclosedherein, and a carrier that can be inert to the compound, can benon-toxic to the skin, and can allow delivery of the compound forsystemic absorption into the blood stream via the skin. The carrier cantake any number of forms such as creams and ointments, pastes, gels, andocclusive devices. The creams and ointments can be viscous liquid orsemisolid emulsions of either the oil-in-water or water-in-oil type.Pastes comprised of absorptive powders dispersed in petroleum orhydrophilic petroleum containing the compound can also be suitable. Avariety of occlusive devices can be used to release the compound intothe blood stream, such as a semi-permeable membrane covering a reservoircontaining the compound with or without a carrier, or a matrixcontaining the compound. Other occlusive devices are known in theliterature.

Compounds described herein can be administered rectally or vaginally inthe form of a conventional suppository. Suppository formulations can bemade from traditional materials, including cocoa butter, with or withoutthe addition of waxes to alter the suppository's melting point, andglycerin. Water-soluble suppository bases, such as polyethylene glycolsof various molecular weights, can also be used.

Lipid formulations or nanocapsules can be used to introduce compounds ofthe present teachings into host cells either in vitro or in vivo. Lipidformulations and nanocapsules can be prepared by methods known in theart.

To increase the effectiveness of compounds of the present teachings, itcan be desirable to combine a compound with other agents effective inthe treatment of the target disease. For example, other active compounds(i.e., other active ingredients or agents) effective in treating thetarget disease can be administered with compounds of the presentteachings. The other agents can be administered at the same time or atdifferent times than the compounds disclosed herein.

Compounds of the present teachings can be useful for the treatment orinhibition of a pathological condition or disorder in a mammal, forexample, a human. The present teachings accordingly provide methods oftreating or inhibiting a pathological condition or disorder by providingto a mammal a compound of the present teachings including itspharmaceutically acceptable salt or a pharmaceutical composition thatincludes one or more compounds of the present teachings in combinationor association with pharmaceutically acceptable carriers. Compounds ofthe present teachings can be administered alone or in combination withother therapeutically effective compounds or therapies for the treatmentor inhibition of the pathological condition or disorder. As used herein,“therapeutically effective” refers to a substance or an amount thatelicits a desirable biological activity or effect. As used herein,“treating” refers to partially or completely alleviating, inhibiting,preventing, and/or ameliorating the condition.

Non-limiting examples of compositions according to the present inventioninclude composition having from about 0.001 mg to about 1000 mg of oneor more 1-N-amino-2-imidazolidinones according to the present inventionand one or more excipients; from about 0.01 mg to about 100 mg of one ormore 1-N-amino-2-imidazolidinones according to the present invention andone or more excipients; and from about 0.1 mg to about 10 mg of one ormore 1-N-amino-2-imidazolidinones according to the present invention andone or more excipients.

The term “effective amount” as used herein means “an amount of one ormore 1-N-amino-2-imidazolidinones, effective at dosages and for periodsof time necessary to achieve the desired or therapeutic result.” Aneffective amount may vary according to factors known in the art, such asthe disease state, age, sex, and weight of the subject being treated.Although particular dosage regimes may be described in examples herein,a person skilled in the art would appreciated that the dosage regime maybe altered to provide optimum therapeutic response. For example, severaldivided doses may be administered daily or the dose may beproportionally reduced as indicated by the exigencies of the therapeuticsituation. In addition, the compositions of the present invention can beadministered as frequently as necessary to achieve a therapeutic amount.

Procedures

The following procedures are utilized in evaluating and selectingcompounds as the Kv1.5 potassium channel inhibitors.

FLIPR L-Type Calcium Channel Assay^(1,2)

HL-1 cells expressing endogenous L-type calcium channels are removedfrom culture flasks using trypsin, plated on fibronectin/gelatin-coated,clear-bottomed, black-walled 96-well microplates in Claycomb media (JRHBiosciences #51800) containing 10% fetal bovine serum, 4 mM L-glutamine,and 10 μM norepinephrine, and grown to confluency overnight. The nextday, growth medium is aspirated from confluent cell monolayers andreplaced with 100 mL per well Tyrode's solution (in mM: 130 NaCl, 4 KCl,1.8 CaCl₂, 1.0 MgCl₂, 20 HEPES, 10 glucose, pH 7.35) and 50 μL per wellFLIPR Calcium Assay kit, component A (#R-8033, Molecular DevicesCorporation) and incubated for 60 min. in a 5% CO₂ 37° C. incubator. 50μL per well test compounds are added to the plates and further incubatedfor 15 min. in a 5% CO₂ 37° C. incubator. All final solutions containthe anion exchange inhibitor, probenecid (2.5 mM). The 96-well platesare then placed in the center position of the FLIPR 1 (FluorometricImaging Plate Reader, Molecular Devices Corporation). Cell monolayers ineach well are simultaneously illuminated at 488 nm with an Argon ionlaser, and fluorescence emission is monitored using a 510-570 nmbandpass filter and a cooled CCD camera. To depolarize the plasmamembrane and activate L-type calcium channels, 50 μL per well of 20 mMKCl (final concentration) are dispensed simultaneously to all 96 wellsusing the FLIPR's automatic 96-well pipettor. Fluorescence measurementsare captured for 5 min. following KCl addition. Calcium influx,expressed as % control, is calculated for each concentration of testcompound and concentration-response curves and IC50 values are generatedusing GraphPad Prism 4.0.

Kv1.5 Patch Clamp EP

Kv1.5 currents are recorded by the whole cell mode of patch clampelectrophysiology.¹ Kv1.5 is stably over expressed in either HEK orLTK-cells. Microelectrodes are pulled from borosilicate glass (TW150)and heat polished (tip resistance, 1.5 to 3 megaohms). The externalsolution is standard Tyrodes solution. The internal (microelectrode)solution contained: 110 mM KCl, 5 mM K₂ATP, 5 mM K₄BAPTA, 1 mM MgCl₂ and10 mM HEPES, adjusted to pH 7.2 with KOH. Command potentials are appliedfor 1 second to +60 mV from a holding potential of −70 mV using Axonsoftware (pClamp 8.1) and hardware (Axopatch 1D, 200B). Compounds areprepared as 10-20 mM DMSO stocks and diluted to appropriate testconcentrations. After stable currents are achieved, compounds areperfused onto the cells and the cells are pulsed every 5 seconds untilno further changes in current are evident at a given compoundconcentration. Inhibition was measured at the end of the 1 second pulsesand expressed relative to controls. Initial Kv1.5 inhibition isestimated by single point determinations done at 1 μM. Concentrationresponse curves are generated for appropriate compounds utilizing atleast four concentrations and an n=3. Curve fitting and IC₅₀ estimatingare done using Graphpad software (Ver. 4).

HERG Patch Clamp EP

HERG currents are recorded by the whole cell mode of patch clampelectrophysiology as described by Hamill et al.³ HERG is stably overexpressed in HEK cells. Microelectrodes are pulled from borosilicateglass (TW150) and heat polished (tip resistance, 1.5 to 3 megaohms). Theexternal solution is standard Tyrodes solution. The internal(microelectrode) solution contained: 110 mM KCl, 5 mM K₂ATP, 5 mMK₄BAPTA, 1 mM MgCl₂ and 10 mM HEPES, adjusted to pH 7.2 with KOH.Command potentials are applied for 2 seconds to +20 mV from a holdingpotential of −80 mV using Axon software (pClamp 8.1) and hardware(Axopatch 1D, 200B). Tail currents are generated by returning to −40 mVfor 2 seconds. Compounds are prepared as 10-20 mM DMSO stocks anddiluted to appropriate test concentrations. After stable currents areachieved, compounds are perfused onto the cells and the cells are pulsedevery 20 seconds until no further changes in current are evident at agiven compound concentration. Inhibition of HERG is measured at the peakof the tail currents and expressed relative to controls. Initial HERGactivity is estimated by single point determinations run at 10 μM.Concentration response curves are generated for appropriate compoundsutilizing at least four concentrations and an n=3. Curve fitting andIC₅₀ estimating are done using Graphpad software (Ver. 4).

-   1. Claycomb W. C. et al., “HL-1 cells: A cardiac muscle cell line    that contracts and retains phenotypic characteristics of the adult    cadiomyocyte.” Proc Natl Acad Sci USA 1998 Mar. 17; 95(6): 2979-84.-   2. Xia M et al., “Functional expression of L- and T-type Ca²⁺    channels in murine HL-1 cells.” J. Mol. Cell Cardiol., 204 January;    3(1): 111-9.-   3. Hamill et al., Pflugers Archiv. 391:85, 1981.

Results for representative compounds according to the present inventionare listed in Table XI below. TABLE XI ¹Kv1.5% ²L-type ³HERG Compoundinhibition Ca²⁺ % Inhib. ¹Kv1.5 ³HERG Number @ 1.0 μM IC₅₀ μM @ 10 μMIC₅₀ nM IC₅₀ μM 1 59 5.5 2 46 3 13 4 72 4.5 53 5 36 6 53 12 29 7 92 4316 232 8 90 15 16 9 90 23 62 689 7.3 10 89 22 57 238 11 95 13 45 12 8238 19 13 83 27 10 14 28 15 46 16 48 17 89 40 22 18 59 24 12 19 27 20 7330 15 21 72 26 57 22 30 23 66 30 21 703 23.6 24 82 10 74 514 6.4 25 8428 31 26 66 17.5 76 716 4.1 27 56 19 63 28 89 16 30 184 10.3 29 85 34 3130 88 3.3 62 31 84 4 32 69 6.7 33 85 35 20 34 98 18 38 35 71 30 14 36 8514 50 37 87 30 6 38 85 5.6 56 39 81 12 40 70 30 1 41 42 42 91 20 90 41843 93 4.3 2 44 60 25 22 45 83 16 55 46 40 47 73 26 65 48 96 9 70 231 3.649 76 23 25 466 11.4 50 79 10 34 233 5.3 51 87 21 20 52 80 16 29 54 8030 46 55 29 29 56 39 57 66 30 12 631 12.4 60 77 10.6 44 453 7.4 61 85 2528 62 26 63 95 6.3 44 64 96 14 55 65 88 31 38 66 86 30 257 12.6 67 90 822 68 60 16 48 69 Not detected 70 22 71 94 13 30 72 81 18 73 62 7 56 65874 85 25 75 Not detected 76 Not detected 77 Not detected 78 75 11 79 6811 70 80 77 20 51 81 78 4 82 72 30 42 83 96 2.8 97 84 67 10 73 570 85 923.3 52 86 20 87 57 6 88 94 11 90 399 89 85 7.6 98 90 74 7 28 91 85 4 9295 30 58 353 5.6 93 46 94 67 13 35 95 43 96 86 1.9 87 97 81 3.5 98 834.8 99 73 4.9 90 100 46 16 92 101 81 19 24 102 6 104 87 21 56 106 74 3017 474 35 107 41 39 1100 54 108 Not detected 109 71 4.6 110 7 111 9 33112 8 113 5 114 75 15 55 115 5 116 Not detected 117 19 118 9 119 80 2 70120 5 121 7 122 36 123 25 124 38 125 42 126 46 127 91 19 54 128 8 19 1294 130 37 131 Not detected 132 3 133 Not detected 134 22 135 53 8 136 44137 4 138 7 139 14 140 6 141 4 142 40 91 143 21 144 16 145 16 11 146 8315 86 147 42 148 2 149 9 150 17 151 8 152 16 153 12 154 7 155 Notdetected 156 7 157 Not detected 158 10 159 4 160 Not detected 161 8 1628 163 16 164 2 165 11 166 41 167 36 168 Not detected 169 16 170 49 30 62171 71 30 55 531 5.8 172 55 9.8 51 173 94 14.6 48 174 9 175 7¹Kv1.5 Patch Clamp EP as described herein²FLIPR L-type Calcium Channel Assay as described herein³HERG Patch Clamp EP as described herein above

The following are additional methods used to determine the suitabilityof the compounds of the present invention for use as Kv1.5 potassiumchannel inhibitors.

In Vivo Test

Vehicle: Compounds are dissolved to a final concentration of 20-50mg/ml, first in dimethyl acetamide (DMAC) then adding the balance ofpropylene glycol 200 (PEG200) for a ratio of DMAC/PEG200 (1:4).

Miniswine: The animals are induced with an IM injection ofketamine/xylazine followed briefly by 1-1.5% isoflurane if needed forintroduction of a line into the vena cava in the neck. Followingintubation, anesthesia is maintained with IV pentobarbital alone withboluses given every 30 minutes during the study. Two electrode-tippedcatheters are introduced via the jugular, one into the right atrium andthe other into the right ventricle. The carotid artery is isolated and atransducer-tipped catheter introduced into the left ventricle. Anincision in the groin is used to access the femoral artery and vein. Theartery is cannulated to monitor arterial pressure at the lower aorta andthe vein is cannulated with an electrode-tipped catheter advanced intothe right atrium. An incision is made above the fourth intercostal spaceand the ribs separated for access to the heart. The pericardium isopened and the left atrium is loosely clamped to the chest wall. Asensing and two pacing electrodes are placed on the atrium. The arterialpressure, ECG, LV pressure, atrial electrogram, body temperature, andexhaled PCO₂ are monitored continuously.

When the surgical preparation is stable, baseline effective refractoryperiods (ERPs) are determined at paced rates of 150, 200, 240, and 300beats per minute from the right and left atriums, and the rightventricle. Compound is then infused over 15 minutes and the ERPdeterminations are repeated starting at the 12th minute of the infusion.The animal is allowed to stabilize, then about 15 minutes after thefirst dose a second dose is given over 15 minutes followed by ERPs. Athird dose may be given. After the final dose the ERPs are determinedevery 15 minutes until the values are back at baseline. Blood samplesare collected at baseline, at the end of each dose, and 15 minutes afterthe final dose.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

1. A compound having Formula I:

wherein R is optionally substituted phenyl; R¹ is optionally substitutedphenyl, optionally substituted C₁-C₆ linear or branched alkyl,optionally substituted C₃-C₇ cycloalkyl, or optionally substitutedheteroaryl; R^(1a) is hydrogen or C₁-C₆ linear or branched alkyl; R² ishydrogen or is selected from: i) —SO₂[C(R^(5a)R^(5b))]_(j)R⁴; ii)—C(O)[C(R^(5a)R^(5b))]_(k)R⁴; or iii) —[C(R^(5a)R^(5b))]_(n)R⁴; R³ ishydrogen or is selected from: i) C₁-C₄ linear or branched alkyl, orC₃-C₇ cycloalkyl; ii) —SO₂[C(R^(5a)R^(5b))]_(j)R⁴; or iii)—[C(R^(5a)R^(5b))]_(n)R⁴; or R² and R³ are taken together with the atomto which they are bound to form an optionally substituted ring havingfrom 3 to 7 ring atoms optionally containing one or more additionalheteroatom ring atoms selected from N, O, or S; R^(5a) and R^(5b) areeach independently hydrogen or C₁-C₄ linear alkyl; R⁴ is selected from;i) hydrogen; ii) —N(R^(6a)R^(b6)); iii) —SO₂R⁷; iv)—C(O)N(R^(8a)R^(8b)); v) optionally substituted C₁-C₆ linear or branchedalkyl, or optionally substituted C₃-C₆ cycloalkyl; vi) optionallysubstituted C₂-C₆ linear or branched alkenyl; vii) optionallysubstituted C₁-C₆ linear or branched alkoxy; viii) optionallysubstituted C₆ or C₁₀ aryl; ix) optionally substituted C₆ or C₁₀aryloxy; x) optionally substituted heteroaryl; xi) optionallysubstituted heterocycle; or xii) optionally substitutedC(O)O(arylalkyl); R^(6a) and R^(6b) are each independently hydrogen,optionally substituted C₁-C₆ linear or branched alkyl, optionallysubstituted C₃-C₆ cycloalkyl, optionally substituted benzyl, optionallysubstituted phenyl, or —C(O)OR^(7a), or R^(6a) and R^(6b) are takentogether with the atom to which they are bound to form a ring havingfrom 3 to 7 ring atoms optionally containing one or more additionalheteroatom ring atoms selected from N, O, or S; R⁷ is hydrogen,optionally substituted C₁-C₆ linear or branched alkyl, optionallysubstituted C₃-C₆ cycloalkyl, or N(R^(7a))₂; R^(7a), at each occurrence,independently, is hydrogen, optionally substituted C₁-C₆ linear orbranched alkyl, or optionally substituted C₃-C₆ cycloalkyl; R^(8a) andR^(8b) are each independently hydrogen, optionally substituted C₁-C₆linear or branched alkyl, optionally substituted C₃-C₆ cycloalkyl, orR^(8a) and R^(8b) are taken together with the atom to which they arebound to form a ring having from 3 to 7 ring atoms optionally containingone or more additional heteroatom ring atoms selected from N, O, or S; Land L¹ are, independently, —[C(R^(9a)R^(9b))]_(m)—; R^(9a) and R^(9b)are, at each occurrence, each independently hydrogen or methyl, orR^(9a) and R^(9b) are taken together with the atom to which they arebound to form a cyclopropyl ring; x and y are independently 0 or 1; m,at each occurrence, independently is 0 to 4; j, at each occurrence,independently is 0 to 4; and k and n, at each occurrence, areindependently 0 to 3; or a pharmaceutically acceptable salt formthereof.
 2. The compound according to claim 1 wherein R^(1a) ishydrogen.
 3. The compound according to claim 1 wherein R is apara-substituted phenyl.
 4. The compound according to claim 1 wherein Ris phenyl, 4-methylphenyl, 4-(fluoromethyl)phenyl,4-(difluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 4-methoxyphenyl,4-(fluoromethoxy)phenyl, 4-(difluoromethoxy)phenyl, or4-(trifluoromethoxy)phenyl.
 5. The compound according to claim 4 whereinR is 4-methoxyphenyl.
 6. The compound according to claim 1 wherein R¹ isa para-substituted phenyl.
 7. The compound according to claim 1 whereinR¹ is phenyl optionally substituted with from 1 to 5 groupsindependently selected from C₁-C₄ linear or branched alkyl optionallysubstituted with halogen, C₃-C₆ cycloalkyl optionally substituted withhalogen, or C₁-C₄ linear or branched alkoxy optionally substituted withhalogen.
 8. The compound according to claim 1 wherein R¹ is3,4-dimethylphenyl, 4-tert-butylphenyl, 4-cyclopropylphenyl,4-diethylaminophenyl, 4-(trifluoromethyl)phenyl, 4-methoxyphenyl,4-(difluoromethoxy)phenyl, or 4-(trifluoromethoxy)phenyl.
 9. Thecompound according to claim 1 wherein R¹ is a substituted phenyl havingthe formula:

wherein R¹⁰ and R¹¹ or R¹¹ and R¹² are taken together with the atoms towhich they are bound to form an optionally substituted ring having from5 to 7 atoms, optionally containing one or more heteroatomsindependently selected from N, O, or S.
 10. The compound according toclaim 9 wherein R¹ is benzo[1,3]-dioxol-4-yl,2-methylbenzo[1,3]dioxol-4-yl, 2,2-difluorobenzo[1,3]dioxol-4-yl,2-methylbenzo[1,3]dioxol-5-yl, 2,2-difluorobenzo[1,3]-dioxol-5-yl,2,3-dihydrobenzo[1,4]dioxin-5-yl,2-methyl-2,3-dihydrobenzo[1,4]-dioxin-5-yl,2-hydroxymethyl-2,3-dihydrobenzo[1,4]dioxin-5-yl,2,3-dihydro-benzo[1,4]dioxin-6-yl,2-methyl-2,3-dihydrobenzo[1,4]dioxin-6-yl, or2-hydroxymethyl-2,3-dihydrobenzo[1,4]dioxin-6-yl.
 11. The compoundaccording to claim 1 wherein R² and R³ taken together with the atom towhich they are bound form an optionally substituted ring having from 3to 7 ring atoms optionally containing one or more additional heteroatomring atoms selected from N, O, or S.
 12. The compound according to claim11 wherein R² and R³ taken together with the atom to which they arebound form optionally substituted dioxidoisothiazolidinyl or optionallysubstituted piperazinyl.
 13. The compound according to claim 1 whereinR⁴ is optionally substituted piperidinyl, optionally substitutedpiperazinyl, optionally substituted pyrazinyl, optionally substitutedpyridinyl, optionally substituted furanyl, optionally substitutedisoxazolyl, optionally substituted quinolinyl, optionally substitutedimidazolyl, or optionally substituted morpholinyl.
 14. The compoundaccording to claim 1 wherein R² is —SO₂[C(R^(5a)R^(5b))]_(j)R⁴ and j iszero.
 15. The compound according to claim 14 wherein R⁴ is—N(R^(6a)R^(6b)), C₁-C₄ optionally substituted linear or branched alkyl,or C₃-C₆ optionally substituted cycloalkyl.
 16. The compound accordingto claim 15 wherein R⁴ is NH₂, methyl, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, ethyl,2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, n-propyl, iso-propyl,cyclopropyl, n-butyl, iso-butyl, tert-butyl, or cyclobutyl.
 17. Thecompound according to claim 16 wherein R⁴ is methyl.
 18. The compoundaccording to claim 14 wherein R⁴ is piperidin-1-yl,4-methylpiperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, ormorpholin-4-yl.
 19. The compound according to claim 1 wherein R² is—SO₂[C(R^(5a)R^(5b))]_(j)R⁴ and j is 1 to
 4. 20. The compound accordingto claim 19 wherein R⁴ is optionally substituted phenyl, optionallysubstituted heterocycle, or optionally substituted heteroaryl.
 21. Thecompound according to claim 19 wherein R² is —SO₂CH₂R⁴ and R⁴ is phenyl,furan-2-yl, isoxazol-5-yl, imidazol-1-yl, pyridin-2-yl, pyridin-3-yl,pyridin-4-yl, or pyrazin-2-yl.
 22. The compound according to claim 1wherein R² is —SO₂[C(R^(5a)R^(5b))]_(j)R⁴, j is 1, R^(5a) and R^(5b) areeach hydrogen, R⁴ is —C(O)N(R^(8a)R^(8b)), and R^(8a) and R^(8b) areeach independently selected from hydrogen methyl, ethyl, n-propyl,iso-propyl, cyclopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, orcyclopropylmethyl.
 23. The compound according to claim 22 wherein R² is—SO₂CH₂C(O)NH₂, —SO₂CH₂C(O)NHCH₃, —SO₂CH₂C(O)N(CH₃)₂,—SO₂CH₂C(O)NH(C₃H₅), or —SO₂CH₂C(O)NHCH₂(C₃H₅).
 24. The compoundaccording to claim 1 wherein R² is —C(O)[C(R^(5a)R^(5b))]_(k)R⁴, k is 0,and R⁴ is optionally substituted C₁-C₄ linear or branched alkyl or C₃-C₆cycloalkyl.
 25. The compound according to claim 24 wherein R⁴ is methyl,fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,dichloromethyl, trichloromethyl, (N-methyl-N-benzyl)aminomethyl,(N-methyl-N-tert-butoxycarbonyl)aminomethyl, ethyl,2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, n-propyl, iso-propyl,cyclopropyl, n-butyl, iso-butyl, tert-butyl, cyclopropylmethyl, orcyclobutyl.
 26. The compound according to claim 1 wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴; R⁴ is optionally substituted C₆ or C₁₀aryl or optionally substituted C₆ or C₁₀ aryloxy; and k is 0 or
 1. 27.The compound according to claim 26 wherein R⁴ is phenyl,4-fluoro-phenyl, 4-chlorophenyl, 4-(trifluoromethyl)phenyl,4-methoxyphenyl, or 4-(trifluoromethoxy)phenyl.
 28. The compoundaccording to claim 1 wherein R² is —C(O)[C(R^(5a)R^(5b))]_(k)R⁴; R⁴ isoptionally substituted C₁-C₁₀ heteroaryl or optionally substitutedC₁-C₁₀ heterocycle; and k is 0 to
 2. 29. The compound according to claim28 wherein R⁴ is furan-2-yl, isoxazol-5-yl, imidazol-1-yl, pyridin-2-yl,pyridin-3-yl, pyridin-4-yl, pyrazin-2-yl, piperidin-1-yl,4-methylpiperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, ormorpholin-4-yl.
 30. The compound according to claim 1 wherein R² is—C(O)[C(R^(5a)R^(5b))]_(k)R⁴; R⁴ is optionally substituted methoxy,optionally substituted ethoxy, optionally substituted n-propoxy,optionally substituted iso-propoxy, optionally substituted n-butoxy,optionally substituted iso-butoxy, or optionally substitutedtert-butoxy; and k is 1 or
 2. 31. The compound according to claim 1wherein R² is —[C(R^(5a)R^(5b))]_(n)R⁴; R⁴ is optionally substitutedaryl, optionally substituted aryloxy, optionally substitutedheterocycle, or optionally substituted heteroaryl; and n is 1 or
 2. 32.The compound according to claim 1 wherein R² is —CH₂R⁴; and R⁴ isquinolin-3-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,4-dimethylaminophenyl, 4-diethylaminophenyl, 4-fluorophenyl,4-chlorophenyl, 4-(imidazol-1-yl)phenyl, or 4-cyanophenyl.
 33. Thecompound according to claim 1 wherein R² is C(O)CH₃, C(O)OCH₃,—C(O)cyclopropyl, C(O)OC(CH₃)₃, C(O)CH₂N(CH₃)benzyl,C(O)CH₂N(CH₃)C(O)OR^(7a), —C(O)furan-2-yl, C(O)C₆H₅, C(O)CH₂C₆H₅,C(O)CH₂OC₆H₅, —C(O)isoxazol-5-yl, —C(O)pyrazin-2-yl, —CH₂(cyclopropyl),CH₂C₆H₅, CH₂CH₂C₆H₅, CH₂C₆H₄(4-CN), CH₂C₆H₄(4-F),—CH₂C₆H_(4[)4-N(CH₃)₂], —CH₂C₆H_(4[)4-N(C₂H₅)₂],—CH₂C₆H_(4[)4-imidazolyl], —CH₂(imidazol-1-yl), —CH₂(pyridine-2-yl),CH₂(pyridine-3-yl), or CH₂(pyridine-4-yl) and R^(7a) is tert-butyl. 34.The compound according to claim 1 wherein R² is SO₂R₄,SO₂CH₂C(O)N(R^(8a)R^(8b)), SO₂[C(R^(5a)R^(5b))]_(j)SO₂—R⁷, orSO₂[C(R^(5a)R^(5b))]_(j)R⁴.
 35. The compound according to claim 1wherein x is 1 and L is —CH₂CH₂—.
 36. The compound according to claim 1wherein x is 1 and L is —CH₂— or —CH₂CH₂CH₂—.
 37. The compound accordingto claim 1 wherein y is 1 and L¹ is —C(R^(9a)R^(9b))—.
 38. The compoundaccording to claim 37 wherein R^(9a) and R^(9b) are each hydrogen. 39.The compound according to claim 37 wherein R^(9a) and R^(9b) takentogether with the atom to which they are bound form cyclopropyl.
 40. Thecompound according to claim 1 wherein y is
 0. 41. The compound accordingto claim 1 wherein x is 1, L is —CH₂CH₂—, and y is
 0. 42. The compoundaccording to claim 1 wherein R² is hydrogen, SO₂,SO₂CH₂C(O)N(R^(8a)R^(8b)), SO₂[C(R^(5a)R^(5b))]_(j)SO₂—R⁷, orSO₂[C(R^(5a)R^(5b))]_(j)R⁴; R⁴ is —NH₂, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃,—CH₂CH₂CH₂CH₂, —CH₂F, —CH₂Cl, —CCl₃, —CH₂CH₂F, —CH₂CHF₂, —CH₂CF₃,-cyclopropyl, —CH═CH₂, CHF₂, CHCl₂, —CH₂CN, -(pyridin-2-yl),-(pyridin-3-yl), -(pyridin-4-yl), or —C₆H₅; R^(8a) is hydrogen, —CH₃,-cyclopropyl, or —CH₂(cyclopropyl); R^(8b) is hydrogen, —CH₃,-cyclopropyl, or —CH₂(cyclopropyl); R^(5a) is hydrogen; R^(5b) ishydrogen; R⁷ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, or-cyclopropyl, and j is 0, 1 or
 2. 43. The compound according to claim 42wherein R³ is hydrogen or methyl.
 44. The compound according to claim 42wherein R and R¹ are independently selected from phenyl optionallysubstituted with from 1 to 5 substituents independently selected fromC₁-C₄ linear or branched alkyl optionally substituted with halogen orC₃-C₆ cycloalkyl, C₃-C₆ cycloalkyl, —OR¹³, —CN, —N(R¹³)₂, —CO₂R¹³,—C(O)N(R¹³)₂, —NR¹³C(O)R¹³, —NO₂, or —SO₂R¹³; and each R¹³ isindependently hydrogen, C₁-C₄ linear or branched alkyl, C₁-C₄ linear orbranched haloalkyl or C₃-C₆ cycloalkyl or two R¹³ units are takentogether with the atom to which they are bound to form a ring comprisingfrom 3-7 ring atoms and optionally containing one or more additionalheteroatoms independently selected from N, O, or S.
 45. The compoundaccording to claim 1 wherein R is phenyl or 4-methoxyphenyl and R¹ is4-tert-butylphenyl, 4-cyclopropylphenyl, 3,4-dimethylphenyl,4-methoxyphenyl, 4-difluoromethoxyphenyl, 4-isopropoxyphenyl,4-(diethylamino)phenyl, benzo[1,3]dioxol-5-yl,2,2-difluorobenzo[1,3]dioxol-5-yl, 2,2-dimethylbenzo[1,3]dioxol-5-yl,2,3-dihydro-benzo[1,4]dioxin-6-yl, 4-difluoromethoxyphenyl, or4-methoxyphenyl.
 46. The compound according to claim 1 wherein thealkyl, benzyl, alkenyl, aryl, aryloxy, alkoxy, heteroaryl, heterocyclegroups are optionally substituted with from 1 to 5 substituentsindependently selected from —OR¹⁵; —C(O)R¹⁵; —C(O)OR¹⁵; —C(O)N(R¹⁵)₂;—N(R¹⁵)₂; —NR¹⁵COR¹⁵; halogen; —SO₂R¹⁵; C₁-C₆ linear or branched alkyloptionally substituted with C₃-C₆ cycloalkyl or halogen; C₃-C₆cycloalkyl; cyano; nitro; oxo; heteroaryl; or heterocycle; wherein twoR¹⁵ units can be taken together with the atom to which they are bound toform a ring comprising from 3-7 ring atoms and optionally containing oneor more additional heteroatoms independently selected from N, O, or S oreach R¹⁵ is independently hydrogen, C₁-C₄ linear or branched alkyl, ₁-C₄linear or branched haloalkyl or C₃-C₆ cycloalkyl.
 47. The compoundaccording to claim 1 wherein R² and R³ are not both hydrogen.
 48. Thecompound according to claim 1 wherein when one of R² and R³ is hydrogenor optionally substituted alkyl, the other of R² and R³ is not hydrogenor optionally substituted alkyl.
 49. The compound according to claim 1wherein when R² or R³ is —[C(R^(5a)R^(5b))]_(n)R⁴, and R⁴ is notaryloxy.
 50. The compound according to claim 1 wherein R² and R³ aretaken together to form an optionally substituted ring having from 3 to 7ring atoms, and R is phenyl optionally substituted by at least onealkoxy substituent.
 51. The compound according to claim 1 having formula(XI):

wherein R is optionally substituted phenyl; R¹ is optionally substitutedphenyl; and R⁴ is selected from; i) hydrogen; ii) optionally substitutedC₁-C₆ linear or branched alkyl or C₃-C₆ cycloalkyl; iii) optionallysubstituted C₆ or C₁₀ aryl; iv) optionally substituted C₁-C₁₀heteroaryl; or v) optionally substituted C₁-C₁₀ heterocycle; or apharmaceutically acceptable salt form thereof.
 52. The compoundaccording to claim 51 wherein R⁴ is methyl, fluoromethyl,difluoromethyl, chloromethyl, dichloromethyl, ethyl,2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, n-propyl, iso-propyl,cyclopropyl, n-butyl, iso-butyl, tert-butyl, cyclobutyl, phenyl,furan-2-yl, isoxazol-5-yl, imidazol-1-yl, pyridin-2-yl, pyridin-3-yl,pyridin-4-yl, and pyrazin-2-yl, piperidin-1-yl, 4-methylpiperidin-1-yl,piperazin-1-yl, 4-methylpiperazin-1-yl, or morpholin-4-yl.
 53. Thecompound according to claim 1 having formula (XIII):

wherein R is optionally substituted phenyl; R¹ is optionally substitutedphenyl; and R^(8a) and R^(8b) are each independently hydrogen, methyl,ethyl, n-propyl, iso-propyl, cyclopropyl, n-butyl, sec-butyl, iso-butyl,tert-butyl, or cyclopropylmethyl; or a pharmaceutically acceptable saltform thereof.
 54. The compound according to claim 1 having formula(XVIII):

wherein R is optionally substituted phenyl; R¹ is optionally substitutedphenyl; and R⁴ is methyl, fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, dichloromethyl, trichloromethyl, amino, methylamino,dimethylamino, aminomethyl, (N-methyl)aminomethyl,(N,N-dimethyl)amino-methyl, (N-methyl-N-benzyl)aminomethyl,(N-methyl-N-tert-butoxycarbonyl)-aminomethyl, ethyl,2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, n-propyl, iso-propyl,cyclopropyl, n-butyl, iso-butyl, tert-butyl, cyclopropylmethyl, orcyclobutyl; or a pharmaceutically acceptable salt form thereof.
 55. Thecompound according to claim 1 having formula (XIX):

wherein R is optionally substituted phenyl; R¹ is optionally substitutedphenyl; and R⁴ is methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy,iso-butoxy, tert-butoxy, phenyl, 4-fluorophenyl, 4-chlorophenyl,4-(trifluoro-methyl)phenyl, 4-methoxyphenyl, 4-(trifluoromethoxy)phenyl,furan-2-yl, isoxazol-5-yl, imidazol-1-yl, pyridin-2-yl, pyridin-3-yl,pyridin-4-yl, pyrazin-2-yl, piperidin-1-yl, 4-methylpiperidin-1-yl,piperazin-1-yl, 4-methylpiperazin-1-yl, or morpholin-4-yl; or apharmaceutically acceptable salt form thereof.
 56. The compoundaccording to claim 1 that is:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-Amino-3-(3-phenylpropyl)-4-(4-methoxyphenyl)-2-imidazolidinone;1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)-2-imidazolidinone;1-Amino-3-[3-(4-methoxyphenyl)propyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-Amino-3-[3-(4-methoxyphenyl)propyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;or1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-difluoromethoxyphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 57. The compoundaccording to claim 1 that is:1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-cyclopropyl)-phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-tert-butyl)benzyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(3-methyl-4-methoxy)phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(3-methoxy-4-methyl)phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-isopropyloxy)-phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(benzo[1,3]dioxol-5-yl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(2,2-difluorobenzo-[1,3]dioxol-5-yl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3-dihydro-benzo[1,4]dioxin-6-yl)]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(2,2-dimethylbenzo-[1,3]dioxol-5-yl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)methyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-chlorophenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-trifluoromethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-diethylamino)-phenyl]-2-imidazolidinone;1-[(Methylsulfonyl)amino]-3-[2-(4-Methoxyphenyl)ethyl]-4-(4-difluoromethoxyphenyl)-2-imidazolidinone;1-[(Methylsulfonyl)amino]-3-[2-(4-Methoxyphenyl)ethyl]-4-(4-trifluoromethoxyphenyl)-2-imidazolidinone;1-[(Methylsulfonyl)amino]-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-(Cyclopropylsulfonylamino)-3-[(4-Methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-(Propylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Butylsulfonylamino)-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Butylsulfonylamino)-3-[(4-methoxyphenyl)-ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-(Vinylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3-dihydrobenzo-[1,4]dioxin-6-yl)]-2-imidazolidinone;1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-tert-butyl-phenyl)-2-imidazolidinone;1-(Fluoromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3dihydrobenzo[b][1,4]dioxin-6-yl)]-2-imidazolidinone;1-(2,2,2-Trifluoroethanesulfonylamino)-4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone;1-(Chloromethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-tert-butyl-phenyl)-2-imidazolidinone;1-(Cyanomethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)]-2-imidazolidinone;1-(Cyanomethylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-methoxy)-phenyl]-2-imidazolidinone;1-[(N-3-Pyridinylmethylsulfonyl)amino]-3-[2-(4-Methoxyphenyl)ethyl]-4-(4-difluoromethoxyphenyl)-2-imidazolidinone.1-[(Phenylmethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(Phenylmethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[(Pyridin-3-yl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[(Pyridin-3-yl)methanesulfonyl]amino-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-imidazolidin-2-one;1-[(Pyridin-3-yl)methylsulfonyl]amino-3-[(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)-2-imidazolidinone;or1-[(Pyridin-3-yl)methylsulfonyl]amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 58. The compoundaccording to claim 1 that is:1-(Aminosulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(4-methoxyphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-cyclopropyl)-phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)-phenyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-tert-butyl)phenyl]-2-imidazolidinone;or1-[(Pyridin-3-yl)methylsulfonyl]amino-3-(3-phenylpropyl)-4-(4-Methoxyphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 59. The compoundaccording to claim 1 that is:1-[(2-Amino-2-oxoethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-{[2-(Cyclopropylamino)-2-oxoethyl]sulfonylamino}-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-({[(2,2-Dimethyl-2-hydroxy-1-methylethyl)amino]-2-oxoethyl}sulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-[[2-(Dimethylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-[[2-(Dimethylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[[2-(Cyclopropylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;(S)-1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-cyclopropylphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[[2-(Cyclobutylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;or1-[[2-[(Bis(methoxyethyl)amino)]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 60. The compoundaccording to claim 1 that is:1-[(Methylsulfonylmethyl)sulfonyl]amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-Cyclopropylphenyl)-2-imidazolidinone;1-[(N-Methyl-N-methylsulfonyl)amino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(N-Methoxyethyl-N-methylsulfonyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;or1-[(N-Methyl-N-phenylsulfonyl)amino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 61. The compoundaccording to claim 1 that is:{2-Oxo-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-imidazolidin-1-yl}-urea;1-(Acetylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethyl-phenyl)-2-imidazolidinone;1-(Acetylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-tert-butyl)benzyl]-2-imidazolidinone;Cyclopropanecarboxylic acid{3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-oxo-imidazolidin-1-yl}-amide;1-Cyclopropanecarbonylamino-4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone;1-(2-Furanoylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Benzoylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;N-{3-[2-(4-Methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-oxo-imidazolidin-1-yl}-2-phenoxyacetamide;N-{3-[2-(4-methoxyphenyl)ethyl]-4-[(3,4-dimethylphenyl)]-2-oxo-imidazolidin-1-yl}-2-phenyl-acetamide;1-(Isoxazol-5-ylcarbonylamino)-3-[2-(4-methoxyphenyl)-ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Isoxazol-5-ylcarbonylamino)-3-[2-(4-methoxyphenyl)-ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-(Methoxycarbonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;2-(Benzylmethylamino)-N-{4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-acetamide;orN-(4-(4-cyclopropylphenyl)-3-(4-methoxyphenethyl)-2-oxoimidazolidin-1-yl)-2-(N,N-dimethylsulfamoyl)acetamide;or a pharmaceutically acceptable salt form thereof.
 62. The compoundaccording to claim 1 that is:1-(Cyclopropylmethylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-Benzylamino-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-Benzylamino-4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone;1-[(4-Fluorophenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(4-Cyanophenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(4-(Dimethylamino)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[(4-(Dimethylamino)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(tert-butyl)phenyl]-2-imidazolidinone;1-[(4-(Dimethylamino)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(Pyridin-2-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(Pyridin-3-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(Pyridin-4-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(Pyridin-4-ylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-(tert-butyl)phenyl)-2-imidazolidinone;1-[(Quinolin-2-ylmethyl)-amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(Phenylethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(4-(1H-imidazol-1-yl)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-N-[2-(Imidazol-1-yl)ethyl]-N-[acetyl]amino-3-[2-(4-methoxyphenyl)ethyl]-4-[(4-tert-butyl)phenyl]-2-imidazolidinone;1-N-[2-(imidazol-1-yl)ethyl]-N-[iso-butyryl]amino-3-[2-(4-methoxyphenyl)-ethyl]-4-[(4-tert-butyl)phenyl]-2-imidazolidinone;or1-[(2-Amino-2-oxoethyl)sulfonylamino]-3-[3-(4-methoxyphenyl)propyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 63. The compoundaccording to claim 1 that is:1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-tert-butylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(R)-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(4-methoxyphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(4-tert-butylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(R)-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(4-methoxyphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(4-tert-butylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-Methoxyphenyl)ethyl]-4-(S)-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(4-methoxyphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(4-tert-butylphenyl)-2-imidazolidinone;or1-(Methylsulfonylamino)-3-(3-phenylpropyl)-4-(S)-(4-cyclopropylphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof
 64. The compoundaccording to claim 1 that is1-Amino-4-[4-(tert-butyl)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-imidazolidinone;1-Amino-4-(4-cyclopropylphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-imidazolidinone:1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-(Sulfamoylamino)-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone;1-Amino-3-[3-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone;1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-[[2-(9H-fluoren-9-ylmethoxy)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[(Phenylmethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[(Pyridin-3-yl)methanesulfonyl]amino-3-[(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-imidazolidin-2-one;4-(3,4-Dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-[(pyridin-4-ylmethyl)amino]-imidazolidin-2-one;{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-carbamicacid tert-butyl ester;4-(3,4-Dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-[(quinolin-3-ylmethyl)-amino]-2-imidazolidinone;1-[[(Dimethylamino)sulfonyl]acetylamino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-{[2-(cyclopropylamino)-2-oxoethyl]sulfonylamino}-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-cyclopropylphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinoneor a pharmaceutically acceptable salt form thereof.
 65. The compoundaccording to claim 1 that is:N-{(4S)-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;tert-butyl[2-({4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}amino)-2-oxoethyl]methylcarbamate;1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-[4-(trifluoromethoxy)phenyl]imidazolidin-2-one;N-{4,4-diethyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-piperazin-1-ylimidazolidin-2-one;N-{3-[2-(4-ethoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-(methylsulfonyl)ethanesulfonamide;2-({4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamoyl)acetamide;4-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N-methylpiperazine-1-carboxamide;N-[4-(4-tert-butylphenyl)-3-(2-{4-[2-(dimethylamino)ethoxy]phenyl}ethyl)-2-oxoimidazolidin-1-yl]methanesulfonamide;1-amino-4-(4-tert-butylphenyl)-3-[3-(4-methoxyphenyl)propyl]imidazolidin-2-one;N-{4-(4-fluorobenzyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;4-(4-tert-butylphenyl)-1-{[2-(1H-imidazol-1-yl)ethyl]amino}-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;N-{4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-pyridin-3-ylacetamide;4-(4-tert-butylphenyl)-1-{[4-(diethylamino)benzyl]amino}-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;4-(4-cyclopropylphenyl)-1-(1,1-dioxidoisothiazolidin-2-yl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;N-{4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-morpholin-4-ylethanesulfonamide;N-{4-(4-methoxyphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-oxoimidazolidin-1-yl}-1-(methylsulfonyl)methanesulfonamide;N-{4-(4-cyclopropylphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-oxoimidazolidin-1-yl}-1-(methylsulfonyl)methanesulfonamide;1-cyano-N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{4-butyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;1-amino-4-(4-fluorobenzyl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;4-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N,N-dimethylpiperazine-1-carboxamide;2-(N-(4-(4-cyclopropylphenyl)-3-(4-methoxyphenethyl)-2-oxoimidazolidin-1-yl)sulfamoyl)-N-(2-(dimethylamino)-2-oxoethyl)-N-methylacetamide;N-{3-[2-(4-methoxyphenyl)ethyl]-2-oxo-4-(1-phenylcyclopropyl)imidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;methyl3-amino-4-({4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}amino)benzoate;N-(cyclopropylmethyl)-2-({(4R)-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamoyl)acetamide;N-{4-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-{[(1-methyl-1H-imidazol-2-yl)methyl]amino}imidazolidin-2-one;N-{4-(4-fluorophenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-pyridin-3-ylmethanesulfonamide;N-{3-[2-(4-methoxyphenyl)ethyl]-2-oxo-4-(1-phenylcyclopropyl)imidazolidin-1-yl}methanesulfonamide;1-amino-4-[4-(2-methoxyethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;N-[3-{2-[4-(difluoromethoxy)phenyl]ethyl}-4-(4-methoxyphenyl)-2-oxoimidazolidin-1-yl]methanesulfonamide;N-{3-[2-(4-methoxyphenyl)ethyl]-2-oxo-4-quinolin-6-ylimidazolidin-1-yl}methanesulfonamide;N-{4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[2-(3,4-dimethoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{4-cyclohexyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;tert-butyl{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}[2-(1H-imidazol-1-yl)ethyl]carbamate;N-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}pyrazine-2-carboxamide;N-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1,1,1-trifluoromethanesulfonamide;N-{3-[2-(4-methoxyphenyl)ethyl]-4-(6-methoxypyridin-3-yl)-2-oxoimidazolidin-1-yl}methanesulfonamide;4-{4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}piperazine-1-carboxamide;N-{4-[4-(2-methoxyethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-[4-(4-methoxyphenyl)-2-oxo-3-{2-[4-(trifluoromethoxy)phenyl]ethyl}imidazolidin-1-yl]methanesulfonamide;N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-(methylsulfonyl)methanesulfonamide;1-amino-3-{2-[4-(difluoromethoxy)phenyl]ethyl}-4-(4-methoxyphenyl)imidazolidin-2-one;1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(1-phenylcyclopropyl)imidazolidin-2-one;N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N-[(1-methyl-1H-imidazol-2-yl)methyl]methanesulfonamide;N-{4-(3,4-dimethoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-1-{[(1-oxidopyridin-4-yl)methyl]amino}imidazolidin-2-one;N-{4,4-diethyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;1-amino-4-[1-(4-fluorophenyl)cyclopropyl]-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;N-{4-[1-(4-fluorophenyl)cyclopropyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-4-methylpiperazine-1-sulfonamide;N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamide;N-[4-(4-tert-butylphenyl)-3-{2-[4-(2-morpholin-4-ylethoxy)phenyl]ethyl}-2-oxoimidazolidin-1-yl]methanesulfonamide;orN-{4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-(dimethylsulfamoyl)acetamide;or a pharmaceutically acceptable salt form thereof.
 66. The compoundaccording to claim 1 that is tert-butyl{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}(quinolin-3-ylmethyl)carbamate;tert-butyl({4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}sulfamoyl)carbamate;1-amino-4-(4-methoxyphenyl)-3-(3-phenylpropyl)imidazolidin-2-one;N-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-N-(phenylsulfonyl)benzenesulfonamide;1-{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-3-phenylurea;1-amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methylphenyl)imidazolidin-2-one;N-{4-butyl-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-1-pyridin-3-ylmethanesulfonamide;1-amino-4-(4-isopropoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;or2-(4-acetylpiperazin-1-yl)-N-{4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}-2-oxoethanesulfonamide;1-[(N-methyl-N-benzylsulfonyl)amino]-3-[2-(4-methoxy-phenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-[(4-(1H-imidazol-1-yl)phenylmethyl)amino]-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-Amino-4-(4-methoxyphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 67. The compoundaccording to claim 1 that is1-Amino-4-(4-cyclopropylphenyl)-3-[3-(4-methoxyphenyl)propyl]-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(3,4-dimethylphenyl)-2-imidazolidinone;1-(Methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(R)-(4-methoxyphenyl)-2-imidazolidinone;N-{(4S)-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;tert-butyl{4-(3,4-dimethylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}(quinolin-3-ylmethyl)carbamate;1-[[2-(Dimethylamino)-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)-ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;1-[[2-[(Bis(methoxyethyl)amino)]-2-oxoethyl]sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;N-{(4R)-4-[4-(difluoromethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{(4S)-4-[4-(difluoromethoxy)phenyl]-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{(4R)-4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;N-{(4S)-4-(4-tert-butylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxoimidazolidin-1-yl}methanesulfonamide;[[[4-(4-cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl]amino]sulfonyl]aceticacid;1-amino-4-(4-methoxyphenyl)-3-[2-(4-methoxyphenyl)ethyl]imidazolidin-2-one;1-(Aminosulfonylamino)-3-[2-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone;1-(Sulfamoylamino)-3-[2-(4-methoxyphenyl)propyl]-4-[(4-methoxy)phenyl]-2-imidazolidinone;1-({[(2,2-Dimethyl-2-hydroxy-1-methylethyl)amino]-2-oxoethyl}sulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;1-[[2-[(Cyclopropylmethyl)amino]-2-oxoethyl]sulfonylamino]-3-[2-(4-cyclopropylphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone;N-{4-(Cyclopropylphenyl)-3-[2-(4-methoxyphenyl)ethyl]-2-oxo-imidazolidin-1-yl}-2-dimethylsulfamoyl-acetamide;or1-[(2-Amino-2-oxoethyl)sulfonylamino]-3-[2-(4-methoxyphenyl)propyl]-4-(4-cyclopropylphenyl)-2-imidazolidinone;or a pharmaceutically acceptable salt form thereof.
 68. A compositioncomprising an effective amount of one or more compounds according toclaim 1 and one or more excipients.
 69. A method for treating orpreventing atrial arrhythmias comprising administering to a subject aneffective amount of a compound according to claim
 1. 70. A method fortreating or preventing thromboembolism, stroke, or cardiac failurecomprising administering to a subject an effective amount of a compoundaccording to claim 1.